Volume 23, Issue 1

newsletter of the myelodysplastic syndromes foundation

www.mds-foundation.org

MDS NEWS HIGHLIGHTS

TABLE OF CONTENTS

FROM THE GUEST EDITOR’S DESK 2

PROFESSIONAL SYMPOSIA

ASH 2016: MDS Breakfast Symposium 8

RESEARCH

International Working Group for 9Prognosis in MDSMDS/MPN International Working Group 10

LITERATURE HIGHLIGHTS 11

NURSING IN MDS 15

FROM THE FOUNDATION

News from Around the World 17

MDS in Focus 19

Social Security and MDS 20

PATIENTS AND CAREGIVERS LIVING WITH MDS FORUMS 21

MDSF MEMBERSHIP 22

AML CORNER 30

MDS CENTERS OF EXCELLENCE 33

OUR CAREGIVER STORIES 38

OUR PATIENT STORIES 40

CONTRIBUTIONS TO THE FOUNDATION

Gifts 46

Memorial Donations 47

Living Endowments 47

14TH INTERNATIONAL SYMPOSIUM ON MDS 52

IN THIS ISSUE

SPRING/SUMMER 2017

PLAN TO ATTEND 14TH INTERNATIONAL SYMPOSIUM ON MYELODYSPLASTIC SYNDROMESMay 3–6, 2017 • Valencia, Spain

FROM THE GUEST EDITOR’S DESK� MicroRNA Signatures in Myelodysplastic Syndrome

Presented by Dr. med. Inga Mandac Rogulj, MDClinics of Hematology and Medical Oncology Clinical Hospital Merkur, Zagreb, Croatia

2017

MDS 2017 will attract an international audience of researchers, clinicians,scientists and educators from around the world who deal with MDS.The MDS 2017 Symposium includes presentations delivered by renownedprofessionals on the latest developments in hematology.

www.mds2017.kenes.com

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a survival median of 8.8 years, to the “veryhigh” group with a survival median of only0.8 years. According to characteristics, thisindex is better than IPSS and it is expectedthat it will be introduced in standardclinical practice.

One curative option in these patients isthe allogeneic transplantation of bonemarrow. However, due to their age, themajority of the patients are not consideredas candidates for this procedure due to thehigh mortality rate related to thetransplantation procedure itself (Koeneckeet al., 2015). The patients are treated withregards to risk stratification. The treatmentoption for patients in the “high” and“INT-2” group is hypomethylating agent5-azacytidine which showed better survival(with survival median of 24.5 months)when compared to the conventionaltherapy (with survival median of 15months) (Fenaux et al., 2009).

On the basis of this study, 5-azacytidinehas been approved by the EuropeanMedicines Agency (EMA). It alsorepresents the gold standard in treating thehigh-risk patients in Croatia.

The low-risk patients are mostfrequently treated by compensations ofblood derivatives. Anemia is the mostfrequent cytopenia and may be treatedsuccessfully with erythropoietic stimu-lating agents (ESAs). Decision about thegroup of patients who should respond toESAs is made after analyzing the IPSS-R,endogenous erythropoietin levels, andtransfusion independence. If ESAtreatment fails, the available options mayinclude lenalidomide, hypomethylatingagents, and clinical trials.

Thrombocytopenia has been treated inexperimental clinical trials withthrombomimetic agents that have showngood efficacy, but still not approved inclinical practice due to some safety

FROM THE GUEST EDITOR’S DESK

Diagnosis of MDS is established on thebasis of cytological puncture, i.e. thebiopsy of bone marrow by defining thesub-type according to the World Healthclassification (Brunning et al., 2008). Thekey medical test is the karyogram due tothe frequency of chromosome anomalies inMDS, and later on due to risk stratification.At the time of diagnosis, the patients aresplit into groups according to the risk forleukemic transformation. The oldest andthe most frequent prognostic index is IPSS(Greenberg et al., 1997). The mentionedindex uses the number of cytopenias,cytogenetic group and number of bonemarrow blasts. It groups the patients in 4special categories with regards to survival:“low” (survival median 5.7 years), “INT-1”(survival median 3.5 years), “INT-2” (1.2years) and “high” (survival median 0.4years). Further importance of this index isbased on the fact that patients are treateddifferently according to the risk group.Recently, the mentioned index is revised inR-IPSS which uses the following variables:hemoglobin, number of neutrophils,number of thrombocytes, 5 cytogeneticgroups, and number of bone marrow blasts(Greenberg et al., 2012). This index splitsthe patients in 5 different groups accordingto survival from the “very low” group with

Myelodysplastic Syndrome –Incidence, Outcomes, ClinicalPicture and Treatment

Myelodysplastic syndrome (MDS)represents the group of malignanthematologic disorders with dysplasia ofone or more blood-forming cells in thebone marrow (Brunning et al., 2008). It isclinically reflected in one or severalcytopenias and with the tendency oftransformation into acute myeloidleukemia (AML). According to theAmerican register SEER, incidence ofMDS is 3.4 cases in 100,000 inhabitantswith the increase of incidence dependingon the age, with the aging median of 76years during the diagnosis (Ma et al.,2007). It is expected that every year morethan 10,000 cases of MDS are diagnosed,which makes it the most frequenthematologic neoplasm in elderly people.Prognosis of these patients is serious, i.e.the possibility that the patient can live up tothree more years is only 35%. The mostfrequent cause of death in these patients istransformation into AML (46.6%),infections (27%) and bleeding (9.8%)(Nachtkamp et al., 2016).

Guest Editorial: MicroRNA Signatures in Myelodysplastic Syndrome

Dr. med. Inga Mandac Rogulj, MDVibor MilunovićMirjana Mariana Kardum ParoSlobodanka Ostojić KolonićClinical Hospital MerkurZagreb, Croatia

GUEST EDITORIAL

Myelodysplastic syndrome

(MDS) represents the

group of malignant

hematologic disorders

with dysplasia of one or

more blood-forming cells

in the bone marrow.

3

concern. Neutropenia in low-risk MDS istaken care of by growth factor support,while the immunosuppressive treatmentsare indicated mainly for pancytopenic,hypoplastic lower-risk MDS. The onlycurrative option is stem cell transplant, andshould be chosen for fit and younger MDSpatients after detailed evaluation of possiblerisks and benefits (Santini, 2016).

(Epi)genetic pathogenesis of MDS

Two studies have tried to definemolecular pathogenesis of MDS. The firststudy included 738 patients with MDS,sequencing 111 genes from peripheralblood or bone marrow (Papaemmanuil etal., 2013). 74% of patients have had at leastone oncogenic mutation, 43% of patientshave had two or more, while 10% ofpatients have had more than threeoncogenic mutations. The frequency ofcertain mutations depended on the timefunction. SFRB1 mutation was an earlyevent which preceded the occurrence ofTET2 mutation (the most frequentmutation at MDS) with consequentialoccurrence of other specific mutations.This scientific discovery has led tohypothesis that clonal or consequentialsub-clonal mutations influence theoutcomes of MDS in the same manner. Thesecond hypothesis was that the number ofgained mutations itself during the diseaseinfluences the outcome. The patients with alarger number of gained “driver” mutationshave had worse outcomes in the light oftotal survival or survival without leukemiatransformation.

On the basis of this study, we mayconclude that MDS by its very nature is atime function of the clonal or sub-clonalmutations, which reflects its dynamicpathogenic flow. The other studydetermined through the molecularproliferation of the frequency of 111 genesin 941 patients with MDS (Haferlach et al.,2014). After multi-variant analysis, 14

genes are included in the model whichcould have anticipated the outcomesindependently from the existing scoreswith genes, which vary from modificationof chromatin to histonic modification.To conclude, the mutations of geneswhich take part in oncogenesis of MDSmay be split into the following groups:RNA modification, DNA methylation,transcription, modification of chromatin,kinases, Cohesin route, RAS route andDNA recovery.

However, with regards to the partlydisappointing scope of human genome, thefocus of scientific circles has moved toepigenome. MDS is a disordercharacterized by aberrant hypomethylationof CpG islands, which is connected tomutation of the TET2 gene responsible forregulation of methylation (Ko et al., 2010).Furthermore, aberrant mutilation differswith regards to the type of MDS, i.e. it ismore expressed in high-risk forms (Jiang etal., 2009). Zhao et al. (2014) haveidentified the model of 6 aberrant mutilatedgenes linked to a worse outcome of thepatients with MDS. The mentioned dataindicate the rationale of the activity of 5-azacytidine in MDS. On the other hand,EZH2, the gene which encodes the histonemethyltransferase, is often mutated inMDS and is connected to worse outcomesby implicating the alternated histonic

modification as one of the events inpathogenesis of MDS (Nikoloski et al.,2010). To conclude, in addition to geneticmutations, epigenetic mutations have asignificant role in the appearance ofmalignant clone and transformation ofMDS to AML. This makes it, according tocertain authors and in our opinion, theprototype of epigenetic disorder (Issa et al.,2013, Milunović et al., 2016).

MicroRNA: History and Function

Pivotal study of microRNA (miRNA)comes from Lee et al. (1993) on the modelof C. elegans. The authors have shown thatlin14 of the gene does not encode protein,but two small molecules of RNA are made,of the size 22 and 61 bases. The smallermolecule links to 3’UTR region of mRNAlin14 gene and inhibits its translation. Thisfinding has been welcomed with doubtsfrom the scientists side, up to the isolationof miRNA gene let7, which linked to3’UTR region of 4 different genes to C.elegans with consequential inhibition andinfluence on physiological development ofthis model (Reinhart et al., 2000). Inhuman conditions, miRNA has firstly beenanalyzed in chronic lymphocytic leukemia(Calin et al., 2002). In patients withmutation 13q14, decreased levels ofmiRNA15 and 16 has been found. Thesestudies brought miRNA in focus of epi-genomics with rapid growth of discoveringnew miRNA in different diseases; so far,3,786 miRNA are known with 22,563targeted genes and 366,181 interactions(Lu et al., 2008, Chou et al., 2016).

The canonical linkage of miRNA linkedto AGO proteins and Dicer within “RNAinduced silencing” complex (RISC) formRNA represents 3’UTR region mRNA(Ha et al. 2014, Milunović et al., 2016).Primary function is the inhibition oftranslation in its initiation during therecognition 5' CAP side of mRNA. RISCwith the help of its numerous proteins alsoleads to inhibition of translation so that it

On the basis of this study

we may conclude that

MDS by its very nature

is a time function of

the clonal or sub-clonal

mutations, which

reflects its dynamic

pathogenic flow.

GUEST EDITORIAL

4

disables 60S ribosome unit in creatingtranslation complex and inhibits 80Scomplex. The other way of inhibitingtranslation through miRNA is deadenylationwith the help of RISC complex. The firstphase is deadenylation, while the secondphase is shortening of poliA tail mRNA.The stated mRNA is stored as inactive incytoplasm, but its dissipation withintracellular exonucleases is also possible.

Circulating MicroRNAClassic paradigm microRNA (miRNA)

was that they are linked to a cell, i.e. thetissue by the occurrence of two pivotaltheses in 2008 (Chim et al., 2008, Lawrie etal., 2008). In the first thesis of Chim et al.(2008), miRNA specific for placentamaternal plasma were found. In the secondthesis it was shown that three miRNA arespecific for diffusion B giant-celllymphoma increased in the serum of thepatients as opposed to healthy controls andtheir prognostic importance is also shown.The authors have claimed that thecirculating miRNA could represent newnon-invasive biomarker at diseases. Thesestudies have posed questions on the originand function of the circulating miRNA(Turchinovich et al., 2012).

In order to avoid degradation fromserum RNA-s, the circulating miRNA inRISC complex may be exported from thecell in the form of micro-vesicles,exosomes and apoptotic bodies (Hunter etal., 2008, Valadi et al. 2007, Zernecke etal., 2009). Surprisingly, the fourth mostfrequent mechanism is independent ofvesicles and is prevalent in circulatingmiRNA; it is also linked to AGO2 proteins(Turchinovich et al., 2011). It should bementioned that for majority of thesetransports the mechanism of regulation isnot known, while miRNA-AGO2 complexis most probably the consequence of celldeath, i.e. they are spontaneously releasedin circulation. Circulating miRNA hasmore functions than inter-cellularcommunication, from immune-modulation

GUEST EDITORIAL

to proliferation and “knockout” cancersuppressor (Pegtel et al., 2010, Mittelbrunnet al., 2011, Skog et al., 2008, Oshima etal., 2010). Function of the largest part ofcirculating miRNA linked to AGO2 proteinis not known. Certain authors make ahypothesis that it does not havephysiologic function with regards to stablekinetics and detection throughout a longerperiod of time (Kosaka et al., 2010). Thisimplicates that the majority of circulatingmiRNA actually reflects the tissue fromwhich it was released, which makes it apotential candidate for non-invasivebiomarker. We have chosen the circulatingmiRNA as a starting point for the proposedproject.

MicroRNA in OncogenesisMiRNA in oncogenesis may be split

into two groups: cancer suppressors andoncogenes (Berindan-Neagoe et al., 2014).One of most frequently studied miRNA,miRNA21, in the mouse model leads topre-oncologic B cell phenotype whichmakes this miRNA to be oncogene (Medinaet al., 2010). On the other side, deletion of13q14 locus in chronic lymphocyteleukemia leads to deletion of LEU2/miR-15a/16-1 group and B clonal proliferation,which indicates miRNA may also be acancer suppressor (Klein et al., 2010).

2014). For example, as a reaction tohypoxia, the induction of transcription ofthe range of miRNA occurs, withconsequential activation of angiogenesis(Kulshreshtha et al., 2008). In proliferation,miRNA 29 and 30 directly inhibitoncogene B myb leading to the senescenceof the cell (Martinez et al., 2011). Ininvasion and metastatic potential on themodel of lung cancer, miRNA 31 leads tomigration, invasion and proliferation(Meng et al., 2013). However, severalpotential hypotheses on regulation and roleof miRNA in oncogenesis should bementioned (Milunović et al., 2016,Berindan-Neagoe et al., 2014 ). As opposedto normal tissues, miRNA is in malignanttissue suppressed, which is attributed togene mutations which encode proteins inits biogenesis. This leads to loss of itsinhibiting role to targeted genes and tooncogenes, facilitating thereby themalignant growth.

In spite of huge progress in the researchof miRNA (number of articles at Medlinedatabase according to MESH abbreviations“microRNA“ and “cancer“ amounts to15,121 including 2,649 of reviews), we areat the very beginning of understanding itsreal role in oncogenesis.

Micro-RNA in Myelodysplastic Syndrome

On the contrary to other malignanthematologic diseases, the research ofmiRNA in MDS is in its early phase.

Expression of miRNA in MDSOne of the pivotal papers in this area

included 25 samples of the bone marrow ofpatients with MDS (Pons et al., 2009). 12enhanced expressed miRNA have beenidentified in bone marrow and 6 inperipheral blood. The majority of thesemiRNA belonged to the miRNA-17-92group, the function of which is implicatedby deregulation of proliferation andantiapoptotic mechanism, which mayprovide explanation for the disordered

In spite of huge progress

in the research of miRNA,

we are at the very

beginning of

understanding its real

role in oncogenesis.

It should be stressed here that miRNAtakes part in almost all characteristics ofthe malignancy from replicative potentialto angiogenesis (Berindan-Neagoe et al.,

5

proliferation of hematopoietic cells inMDS. In the further analysis, 6 miRNAwere expressed and in the samples ofperipheral blood implicating thatperipheral blood may reflect thecompartment of the bone marrow (Pons etal., 2009), 3 miRNA (miRNA 181a, 222and 155) were intensively expressed inMDS of high risk as opposed to their lowexpression in MDS of low risk. In otherresearch, as well as in other neoplasms,smaller expression of miRNA in MDSsamples has been noticed, but the miRNA-1/miRNA-133a group was intensivelyexpressed in all samples (Hussein et al.,2010). With regards to chromosomeanomalies, only MDS del5q had a differentmiRNA profile; however, due to itsspecifics and different biology of MDSdel5q, this is not an expected finding andwe will not refer to this disorder anylonger. Dostalova et al. (2011) haveidentified 13 intensively expressed miRNAand 9 decreasingly expressed miRNA. Inthe further analysis the patients were splitinto RAEB 1 (MDS of low risk), RAEB 2(MDS of high risk) and AML. Profile ofRAEB 1 was similar to healthy controls;RAEB 2 was similar to AML. The authorshave separated two miRNA; miRNA 10-aand 34-a. MiRNA 10-a was linked toleukemia transformation in RAEB 2 sub-type, while miRNA34-a was linked toalteration of hematopoiesis. This is also thefirst study which showed pathogeneticmechanism of miRNA in MDS. Erdoganet al. (2011) have analyzed 44,519miRNA probes in low-risk MDS. 5miRNA remained significantly invalidation group with constructedalgorithm of even 50 targeted genes whichvaried from transcription regulation toRNA translation, showing that a smallnumber of miRNA may target multiplemRNA of targeted genes. Choi et al.(2015) conducted a research on theinfluence of trisomy 8 and 1q, of frequentchromosome abnormalities in MDS, to theexpression of miRNA. Significant

elevation of miRNA-194-5p and miRNA-320a has been found in these patients withpossible prognostic implication for miRNA-194-5p. In Pons et al., 25 patients with MDSidentified the intensified expression of 12miRNA in bone marrow55. Furthermore, 6of these miRNA were also expressed inperipheral blood.

miRNA-mRNA interactions in MDS

As it is presented, the expression ofmiRNA is aberrantly changed in MDS, butto understand the real pathogenesismiRNA-mRNA interaction should beunderstood. Only several studies assessedthis role in MDS. Inefficient erythropoiesisis linked to miRNA21 in MDS throughSMAD7 inhibition, i.e. activation of TGF-2 route (Bhagat et al., 2013). The otherstudy tested the relation of miRNA22 andTET2 genes, frequently mutated in MDSon the mouse model (Song et al., 2013).In miRNA22 transgenic mice a lowconcentration of 5-hmC was recorded,implicating a disordered methylation andaberrant hematopoesa (self-regeneration,displasion) developing into MDS or AML.As a targeted gene, TET2 cancersuppressor gene appeared, implicating thatcontrary to previous papers where itsmutation was significant, the inhibitionmay be a lot more subtle at epigenetic level(Papaemmanuil et al., 2013, Haferlach etal., 2014). Arabanian et al. (2014) hasshown that miRNA-23a is directly linkedto 3'UTR region of CXCL12 mRNA,leading to inhibition of the activation ofTGFB1 route and proliferation ofhematopoietic cells on the model of the cellcultures and human cells.

Prognostic Meaning of miRNAin MDS

So far in this bibliographical review, wehave shown that miRNA and its role aredisturbed in MDS; however, due to thesmall number of studies, the exact functionof miRNA remains relatively unknown in

its pathogenesis. Furthermore, a questionarises whether miRNA has any kind ofclinical meaning in this context. Sokol et al.(2011) have managed in the sample of 44MDS patients to find the miRNA profile,which included 10 different miRNA. Thisprofile could have split the patients perIPSS scoring system to high-risk and low-risk patients. MicroRNA181B was moreexpressed in high-risk group; but the studywas particularly interesting because itsintensified expression in the low-risk groupwas linked to the worse survival (3.5versus 9.3 years). Sokol et al suggested thatanalysis of the microRNA expressionprofile offers diagnostic utility, andprovides pathogenetic and prognosticdiscrimination in MDS.

The previously described study by Songet al. (2013) on interaction of TET2 cancersuppressor and miRNA22 also included thegroup of 107 patients. MiRNA22 showed astrong correlation with decrease ofexpression of TET2 which indirectly hadan influence on the total survival. The firststudy, which used the circulating miRNA(let 7a and miRNA 16) in the plasm of 50MDS patients found the bi-modaldistribution of expression of thesebiomarkers (Zuo et al., 2011). In the further

GUEST EDITORIAL

In this bibliographical

review, we have shown

that miRNA and its role

are disturbed in MDS,

However, due to the

small number of studies

the exact function of

miRNA remains

relatively unknown in

its pathogenesis.

6

analysis, the authors have split the patientsinto two groups with regards to the level ofexpression. High levels of these biomarkerswere linked to the worse outcome in thelight of total survival and survival withoutleukemia transformation, while let 7a inmulti-variant analysis was an independentfactor. The largest study in this area used800 probes of human circulating miRNAon 72 patients with MDS with normalkaryogram (Zuo et al., 2015). The profileof 7 miRNA has been found (let 7a,miRNA 144, 16, 25, 451, 651 and 655)which could have split the patients withregards to the outcome into two groupswith the risk to death totaling 6.54%.Furthermore, this profile could haveanticipated the outcome with higherprecision (75%) of the IPSS scoring systemitself (50%). According to this biblio-graphical overview, we have found onlyone study which used miRNA as aprognostic factor for treatment withhypomethylating agents 5-azacytidine anddecitabine. The study included 58 patientswith primary outcome of the total response(Kim et al., 2014). The patients werestratified according to the expression ofcirculating miRNA21 into two groups. Thegroup with high expression had asignificantly lower rate of responses (41.2%)in comparison to the group with lowexpression (73.2%) with sensitivity of83.3% and specificity of 45.8% for thestated biomarker. There is no significantdifference in total survival, but the time

without leukemia transformation wassignificantly longer in the group with lowexpression of miRNA 21 (44.5 versus 14months).

The field of microRNA research seemsto be very complex, but may also open newhorizons in pathophysiology, diagnosticand therapeutic options in MDS.

References:

01. Arabanian LS, Fierro FA, Stölzel F et al.MicroRNA-23a mediates post-transcrip-tional regulation of CXCL12 in bonemarrow stromal cells. Haematologica.2014;99:997-1005.

02. Berindan-Neagoe I, Monroig Pdel C,Pasculli B. et al. MicroRNAome genome:a treasure for cancer diagnosis and therapyCA Cancer J Clin. 2014;64:311-36.

03. Bhagat TD, Zhou L, Sokol L et al. miR-21mediates hematopoietic suppression inMDS by activating TGF-β signaling.Blood. 2013;121:2875-81.

04. Brunning RD, Orazi A, Germing U.Myelodysplastic syndromes/neoplasms,overview. U: Swerdlow SH, Campo E,Harris NL, et al. WHO classification oftumors of hematopoietic and lymphoidtissues. Lyon: IARC press; 2008.

05. Calin GA, Dumitru CD, Shimizu M et al..Frequent deletions and down-regulation ofmicro- RNA genes miR15 and miR16 at13q14 in chronic lymphocytic leukemia.Proc Natl Acad Sci USA. 2002;99:15524-9.

06. Cheson BD, Greenberg PL, Bennett JM etal. Clinical application and proposal formodification of the International WorkingGroup (IWG) response criteria inmyelodysplasia. Blood. 2006;108:419-25.

07. Chim SS, Shing TK, Hung EC et al.Detection and characterization of placentalmicroRNAs in maternal plasma. ClinChem. 2008;54:482-90.

08. Choi JS, Nam MH, Yoon SY, Kang SH.MicroRNA-194-5p could serve as adiagnostic and prognostic biomarker inmyelodysplastic syndromes. Leuk Res.2015 l;39:763-8.

09. Chou CH, Chang NW, Shrestha S et al.miRTarBase 2016: updates to theexperimentally validated miRNA-target

interactions database. Nucleic Acids Res.2016;44:D239-47

10. Dostalova Merkerova M, Krejcik Z,Votavova H, et al. Distinctive microRNAexpression profiles in CD34+ bonemarrow cells from patients withmyelodysplastic syndrome. Eur J HumGenet. 2011;19:313-9.

11. Erdogan B, Facey C, Qualtieri J, et al.Diagnostic microRNAs in myelodys-plastic syndrome. Exp Hematol. 2011;39:915-926.

12. Fenaux P, Mufti GJ, Hellström-Lindberg Eet al. Efficacy of azacitidine comparedwith that of conventional care regimens inthe treatment of higher-risk myelodys-plastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223-32.

13. Greenberg P, Cox C, LeBeau MM et al.International scoring system for evaluatingprognosis in myelodysplastic syndromes.Blood. 1997;89:2079-88

14. Greenberg PL, Tuechler H, Schanz J et al.Revised international prognostic scoringsystem for myelodysplastic syndromes.Blood. 2012;120:2454-65

15. Ha M, Kim VN. Regulation of microRNAbiogenesis. Nat Rev Mol Cell Biol. 2014;15:509-24.

16. Haferlach T, Nagata Y, Grossmann V et al.Landscape of genetic lesions in 944patients with myelodysplastic syndromes.Leukemia. 2014;28:241-7.

17. Hunter MP, Ismail N, Zhang X et alDetection of microRNA expression inhuman peripheral blood microvesicles.PLoS One. 2008;3:e3694

18. Hussein K, Theophile K, Büsche G et al.Aberrant microRNA expression pattern inmyelodysplastic bone marrow cells. LeukRes. 2010;34:1169-74.

19. Issa JP. The myelodysplastic syndrome asa prototypical epigenetic disease. Blood.2013;121:3811-7.

20. Jiang Y, Dunbar A, Gondek LP et al.Aberrant DNA methylation is a dominantmechanism in MDS progression to AML.Blood. 2009;113:1315-25.

21. Kim Y, Cheong JW, Kim YK et al. SerummicroRNA-21 as a potential biomarker for

GUEST EDITORIAL

The field of microRNA

research seems to be

very complex, but may

also open new horizons

in pathophysiology,

diagnostic and therapeutic

options in MDS.

7

response to hypomethylating agents inmyelodysplastic syndromes. PLoS One.2014;9:e86933.

22. Klein U, Lia M, Crespo M et al TheDLEU2/miR-15a/16-1 cluster controls Bcell proliferation and its deletion leads tochronic lymphocytic leukemia. CancerCell. 2010;17:28-40

23. Ko M, Huang Y, Jankowska AM et al.Impaired hydroxylation of 5-methyl-cytosine in myeloid cancers with mutantTET2. Nature. 2010;468:839-43.

24. Koenecke C, Göhring G, de Wreede LC etal. Impact of the revised InternationalPrognostic Scoring System, cytogeneticsand monosomal karyotype on outcomeafter allogeneic stem cell transplantationfor myelodysplastic syndromes andsecondary acute myeloid leukemiaevolving from myelodysplastic syndromes:a retrospective multicenter study of theEuropean Society of Blood and MarrowTransplantation. Haematologica. 2015;100:400-8.

25. Kosaka N, Iguchi H, Ochiya T. CirculatingmicroRNA in body fluid: a new potentialbiomarker for cancer diagnosis andprognosis. Cancer Sci. 2010;101:2087-92

26. Kulshreshtha R, Davuluri RV, Calin GA,Ivan M. A microRNA component of thehypoxic response. Cell Death Differ.2008; 15:667-71.

27. Lawrie CH, Gal S, Dunlop HM et alDetection of elevated levels of tumour-associated microRNAs in serum ofpatients with diffuse large B-celllymphoma. Br J Haematol. 2008;141:672-5.

28. Lee RC, Feinbaum RL, Ambros V. The C.elegans heterochronic gene lin-4 encodessmall RNAs with antisense comple-mentarity to lin-14. Cell. 1993;75: 843-54.

29. Lu M, Zhang Q, Deng M et al An analysisof human microRNA and diseaseassociations. PLoS One. 2008;3:e3420.

30. Ma X, Does M, Raza A, Mayne ST.Myelodysplastic syndromes: incidenceand survival in the United States. Cancer.2007;109:1536-42.

31. Martinez I, Cazalla D, Almstead LL, SteitzJA, DiMaio D. miR-29 and miR-30regulate B-Myb expression during

cellular senescence. Proc Natl Acad SciUSA. 2011;108:522-7.

32. Milunović V, Mandac Rogulj I, Planinc-Peraica A, Bulycheva E, Kolonić OstojićS. The role of microRNA inmyelodysplastic syndromes: beyond DNAmethylation and histone modification. EurJ Haematol. 2016;96:553-63.

33. Meng W, Ye Z, Cui R et al. MicroRNA-31predicts the presence of lymph nodemetastases and survival in patients withlung adenocarcinoma. Clin Cancer Res.2013;19:5423-33.

34. Medina PP, Nolde M, Slack FJ. OncomiRaddiction in an in vivo model ofmicroRNA-21-induced pre-B-cell lym-phoma. Nature. 2010;467:86-90.

35. Mittelbrunn M, Gutiérrez-Vázquez C,Villarroya-Beltri C et al. Unidirectionaltransfer of microRNA-loaded exosomesfrom T cells to antigen-presenting cells.Nat Commun. 2011;2:282.

36. Nachtkamp K, Stark R, Strupp C et al.Causes of death in 2877 patients withmyelodysplastic syndromes. Ann Hematol.2016;95:937-44.

37. Nikoloski G, Langemeijer SM, Kuiper RPet al. Somatic mutations of the histonemethyltransferase gene EZH2 in myelo-dysplastic syndromes. Nat Genet. 2010;42:665-7.

38. Ohshima K, Inoue K, Fujiwara A et al Let-7 microRNA family is selectively secretedinto the extracellular environment viaexosomes in a metastatic gastric cancercell line. PLoS One. 2010 Oct 8; 5:e13247.

39. Papaemmanuil E, Gerstung M, MalcovatiL et al. Clinical and biological implicationsof driver mutations in myelodysplasticsyndromes. Blood. 2013;122:3616-27

40. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA et al. Functional delivery ofviral miRNAs via exosomes. Proc NatlAcad Sci USA. 2010;107:6328-33

41. Pons A, Nomdedeu B, Navarro A et al.Hematopoiesis-related microRNAexpression in myelodysplastic syndromes.Leuk Lymphoma. 2009;50:1854-9.

42. Reinhart BJ, Slack FJ, Basson M et al. The21-nucleotide let-7 RNA regulatesdevelopmental timing in Caenorhabditiselegans. Nature. 2000;403:901-6.

43. Santini V. Treatment of low-risk myelo-dysplastic syndromes. ASH EducationBook. 2016. vol. 2016 no.1;462-469

44. Skog J, Würdinger T, van Rijn S et al.Glioblastoma microvesicles transportRNA and proteins that promote tumourgrowth and provide diagnostic bio-markers. Nat Cell Biol. 2008;10:1 470-6.

45. Sokol L, Caceres G, Volinia S, Alder H,Nuovo GJ et al. Identification of a riskdependent microRNA expressionsignature in myelodysplastic syndromes.Br J Haematol. 2011 Apr;153(1):24-32.

46. Song SJ, Ito K, Ala U et al. The oncogenicmicroRNA miR-22 targets the TET2tumor suppressor to promote hemato-poietic stem cell self-renewal andtransformation. Cell Stem Cell. 2013;13:87-101

47. Turchinovich A, Weiz L, Langheinz A,Burwinkel B. Characterization of extra-cellular circulating microRNA. NucleicAcids Res. 2011;39:7223-33.

48. Turchinovich A, Weiz L, Burwinkel B.Extracellular miRNAs: the mystery oftheir origin and function. Trends BiochemSci. 2012;37:460-5.

49. Valadi H, Ekström K, Bossios A, SjöstrandM, Lee JJ, Lötvall JO. Exosome-mediatedtransfer of mRNAs and microRNAs is anovel mechanism of genetic exchangebetween cells. Nat Cell Biol. 2007;9:654-9.

50. Zernecke A, Bidzhekov K, Noels H et al.Delivery of microRNA-126 by apoptoticbodies induces CXCL12-dependentvascular protection. Sci Signal. 2009;2:ra81.

51. Zhao C, Lu F, Chen H et al. Clinicalsignificance of circulating miRNAdetection in lung cancer. Med Oncol.2016;33:41.

52. Zuo Z, Calin GA, de Paula HM et al.Circulating microRNAs let-7a and miR-16predict progression-free survival andoverall survival in patients with myelo-dysplastic syndrome. Blood. 2011;118:413-5.

53. Zuo Z, Maiti S, Hu S et al. Plasmacirculating-microRNA profiles are usefulfor assessing prognosis in patients withcytogenetically normal myelodysplasticsyndromes. Mod Pathol. 2015;28:373-82.

GUEST EDITORIAL

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MEETING HIGHLIGHTS AND ANNOUNCEMENTS

On behalf of the MDS Foundation and our Board of Directors, THANK YOU for joining our BreakfastSatellite Symposium!Another great MDSF Symposium #ASH16!

It’s so great to see such a full house when there is somuch progress to be made in the field of MDSresearch!

HIGHLIGHTS FROM THE AMERICAN SOCIETY OF HEMATOLOGY 58TH ANNUAL MEETING & EXPOSITION • DECEMBER 2016

We just can’t stop reliving our amazing symposium turn out at the American Society ofHematology's 58th Annual Meeting! Crowd of 800+ hematologists participated in our sponsoredsatellite symposium.

A special THANK YOU to our Board of Directors for their continued support and excellentefforts in MDS!

PRESENTATIONS AVAILABLEMDS Foundation Website: http://www.mds-foundation.org/ash-breakfast-2016/

PRESENTATIONS

NOW AVAILABLE

Revised International PrognosticScoring System (IPSS-R) for

Myelodysplastic Syndromes

Risk Assessment Calculator

© MDS Foundation. All rights reserved.

9

INTERNATIONAL WORKING GROUPSMDS FOUNDATION INTERNATIONAL WORKING GROUP FOR PROGNOSIS IN MDS

Latest News Regardingthe Molecular MutationProject of the IWG-PMMutations Predict PrognosisIndependent of the IPSS-R: Overview

The International Prognostic ScoringSystem (IPSS) and IPSS-R were developedby the International Working Group forPrognosis in MDS (IWG-PM) under theaegis of the MDS Foundation and havebecome the dominant clinical tools forpredicting prognosis in patients withmyelodysplastic syndromes (MDS).1 Aprognostic scoring system that integratesgene mutations into the known criticalclinical features would have great additiveutility for improved determination ofprognosis in patients with MDS and has thepotential for widespread clinical use. Theongoing project of the IWG-PM MolecularCommittee (IWG-PM-M) has shown, withthe IPSS-R and other scoring systems, usinglarger molecularly characterized datasets,that mutations are independent predictorsof patients’ overall survival. This findingjustifies a prognostic scoring system thatwill integrate clinical and genetic features.

Prognostic Impact of TP53Mutations

A central aim of the IWG-PMMolecular project is to develop a largedatabase of MDS patients with deepclinical annotation and genetic sequencingdata for clinical, biologic and possiblytherapeutic purposes. In addition to theanalysis of previous samples, sequencingadditional MDS cases will be performed tofurther develop the database.

As a first project for the IWG-PMmolecular database, the impact of TP53mutations in MDS demonstrated that thisstatus divides MDS patients with complexkaryotypes into distinct prognostic riskgroups, with those carrying the mutationhaving poorer prognoses. Despite theirstrong associations with adverse clinical andcytogenetic abnormalities that are alreadyincorporated into existing prognosticscoring systems, TP53 mutations carrysignificant independent prognostic value fordecreased survival for patients with MDS.

This work was presented by Dr. RafaelBejar at the 2014 American Society ofHematology Meeting2 with updating at the2015 13th International MDS FoundationSymposium held in Washington, D.C.

Recent Molecular ResultsRecently, molecular and clinical data on

3392 MDS patients gathered by membersof the IWG-PM-Molecular Committeewere combined and analysed and theabstract describing these findings waspresented for oral presentation at the 2015ASH Annual Meeting in Orlando.3Survival data were available for 3200patients. The 27 genes sequenced in at leasthalf of the cohort and mutated in >1.5% ofsamples were included for analysis.Mutations in 12 genes were stronglyassociated with shorter overall survival inunivariate analyses. The large size of thecohort allowed for more precise estimatesof survival in the less frequently mutatedgenes. IPSS-R risk groups could bedetermined for 2173 patients and werestrongly associated with survival. Adjustingthe hazard ratio of death for IPSS-R riskgroups identified several mutated geneswith independent prognostic significance.Patients without mutations in any of themajor adverse genes represented over halfof the fully sequenced cohort and had alonger median survival than patients withadverse mutations even after correction forIPSS-R risk groups. A mutation scorebased on survival risk will be proposed andinternally validated. The impact of somaticmutations in patients traditionallyconsidered lower risk will also be explored. Current Project Status, Plans forSequencing of New Samples

In addition to the above assessment ofprevious samples, led by Dr ElliPapaemmanuil, the project is sequencingadditional large numbers of MDS cases tofurther develop our database andmutational evaluations. An automatedsample management system was recentlyimplemented that links sample reception tolibrary preparation and sequencingsubmission. The results of these analyseswill serve as the template with which to buildan integrated molecular risk model for MDS.

References1.Greenberg PL, Tuechler H, Schanz J, et al.

Revised international prognostic scoringsystem for myelodysplastic syndromes. Blood.2012;120:2454–2465.

2.Bejar R, Papaemmanuil E, Haferlach T, Garcia-Manero G, Maciejewski JP, Sekeres MA, WalterMJ, Graubert TA, Cazzola M, Malcovati L,Campbell PJ, Ogawa S, Boultwood J, Bowen D,Tauro S, Groves M, Fontenay M, Shih L-Y,Tuechler H, Stevenson D, Neuberg D,Greenberg PL, Ebert BL. TP53 Mutation StatusDivides MDS Patients with Complex Karyo-types into Distinct Prognostic Risk Groups:Analysis of Combined Datasets from the IWG-PM-Molecular Prognosis Committee. Proc AmSoc Hematology, San Francisco, December,2014, abstract, Blood. 2014;124(21):#532.

3.Bejar R, Papaemmanuil E, Haferlach T, Garcia-Manero G, Maciejewski JP, Sekeres MA, WalterMJ, Graubert TA, Cazzola M, Malcovati L,Campbell PJ, Ogawa S, Fenaux P, Hellström-Lindberg, Kern W, Boultwood J, Pellagatti A,Bowen D, Tauro S, Groves M, Vyas P, Quek L,Nazha A, Thol F, Heuser M, Shih L-Y, PadronE, Sallman D, Komrojki R, List A, Santini V,Fontenay M, Campbell P, Tuechler H, StevensonD, Neuberg D, Greenberg P, Ebert BL. SomaticMutations in MDS Patients Are Associated withClinical Features and Predict Prognosis Inde-pendent of the IPSS-R: Analysis of CombinedDatasets from the IWG-PM-MolecularCommittee, ASH 2015 abstract, Orlando,December 2015. Blood. 2015;126(23), #907.

DOWNLOADOUR FREE APPIPSS-R Calculators(Basic and Advanced)

Available Online and at the App Store

This global project is being coordinated by BenEbert and Peter Greenberg (co-Chairs), RafaelBejar and Ellie Papaemmanuil, with statisticalsupport by Donna Neuberg, Kristin Stevensonand Heinz Tuechler.

10

Myelodysplastic syndromes represent aheterogeneous group of disease entitieswith diverse clinical features, geneticcomposition, natural history, and responseto therapy. Mounting evidence has suggestedthat several MDS ‘subtypes’ are distinctenough that they should be consideredunique disease entities. To this end, in 2008the World Health Organization designatedfour clinical entities to be recognized asbona fide diseases with overlappingdysplastic and proliferative features. Theseinclude Chronic Myelomonocytic Leukemia(CMML), atypical CML (aCML), JuvenileMyelomonocytic Leukemia (JMML), andMyelodysplastic/MyeloproliferativeNeoplasms Unclassifiable (MDS/MPN-U).Since this reclassification, many investi-gations have confirmed the unique molecularunderpinnings and clinical trajectories ofeach of these diseases. However, thisstratification has resulted in rare diseases thatrequire collaborative efforts to maketransformative changes in patient care.

The MDS/MPN International WorkingGroup (MDS/MPN IWG) was originallydeveloped in 2012. The work of this initialgroup resulted in the first two peer-reviewed publications. By the end of 2013,membership was expanded to include aCMML multi center project, and the groupenlisted the support of the MDS Foundation.The overarching goal of this group is toidentify key knowledge gaps in the area ofMDS/MPNs and facilitate international,collaborative, translational science geared torapidly improve our understanding of thesefatal neoplasms. The current membershipincludes 32 investigators, from 20 centers,across 7 countries.

Work from collaborations within thisgroup has resulted in several peer-reviewedpublications:� A consensus recommendation for

response criteria that sets the foundationfor a common endpoint across manyMDS/MPN clinical trials.2

� A consensus review on the biology andclinical presentation of MDS/MPNs.2

erative neoplasms (MDS/MPN) in adults.Blood. 2105;125:1857-1865, doi:10.1182/blood-2014-10-607341.

2. Mughal TI, et al. An International MDS/MPN Working Group’s perspective andrecommendations on molecular pathogenesis,diagnosis and clinical characterization ofmyelodysplastic/myeloproliferative neo-plasms. Haematologica. 2105;100:1117–1130,doi:10.3324/haematol.2014.114660.

3. Padron E. et al. An international data set forCMML validates prognostic scoring systemsand demonstrates a need for novel prognos-tication strategies. Blood Cancer. 2015;5,e333, doi:10.1038/bcj.2015.53.

� The development of an internationalCMML dataset that includes clinical andmolecular data.3

Ongoing collaborations underway include:� Expansion and prospective molecular

sequencing of the international CMMLdata set.

� Exploring the consequence of anMDS/MPN diagnosis on quality of life.

� Identify/Generating a consensus CMMLprognostic model.

� Exploring the role of transplant inmolecularly defined CMML subtypes.

� Implementing international clinicaltrials on both sides of the Atlantic.

References:1. Savona MR, et al. An international

consortium proposal of uniform responsecriteria for myelodysplastic/myeloprolif-

MAKING CONNECTIONS AROUND THE WORLD

The MDS/MPN International Working Group

LAUNCHING THE INITIAL GROUP CLINICAL STUDY IN 2018MDS/MPN Committee Develops NL-MARRO: A Study of Novel Therapies in MDS/MPN

The MDS/MPN IWG, founded in 2012, is focused on understanding MDS/MPN anddeveloping new therapy to improve the survival and reduce morbidity in these diseases.The MDS Foundation MDS/MPN Committee has supported the IWG's mission and afterpublishing proposed response criteria in the treatment of MDS/MPN in 2015 (Savona, etal. Blood 2015), now is poised to launch the initial group clinical study in 2018. Noveltherapy combinations in untreated MDS/MPN And Relapsed/Refractory Overlap Syndromes(NL-MARRO) is a a Phase II Basket Trial of Novel Combination Therapies in MDS/MPNpatients naïve to therapy or who fail primary therapy with DNMTi (DNA methyltransferaseinhibitors). This is first study testing the MDS/MPN IWG response criteria for all MDS/MPN,with goals:

1. To test new therapies in MDS/MPN2. To validate/update the MDS/MPN Response Criteria3. To develop biomarkers for response to therapy in MDS/MPN4. To improve understanding of MDS/MPN

The MDSF MDS/MPN Subcommittee on Clinical Trials, led by Michael Savona, VanderbiltUniversity Medical Center, is building the infrastructure to conduct clinical trials in MDS/MPNat clinical sites that have developed local expertise diagnosing and treating MDS/MPN. Thiswill allow MDSF clinical investigators in the US and Europe to cooperatively test promisingtherapies in a multi-institutional platform. Novel compounds which have completed safetyassessment and dose finding experiments, typically with early efficacy signals in othermyeloid disease, will be considered by the Subcommittee for NL-MARRO. Investigators arededicated to data compliance for development of risk prognostication and stratification,enrollment of patients per WHO criteria, refine pathology/response criteria/treatment forMDS/MPN (eg central path), and refinement via regularly scheduled MDSF-sanctionedplanning meetings. All interested investigators are welcome.

1111

Highlights of Latest Literature in MDS Suneel D. Mundle, PhDRhea Mundle

Listed below are citations of some newpublications relevant to MDS (pathogenesis,clinical characterization, management, etc.).To access the complete articles log on towww.pubmed.gov.

ePIDeMIOlOgy, DIAgNOSISAND PROgNOSIS:1. Bennett JM. Changes in the updated

2016: WHO classification of themyelodysplastic syndromes and relatedmyeloid neoplasms. Clin LymphomaMyeloma Leuk. 2016;16(11):607-609.(https://www.ncbi.nlm.nih.gov/pubmed/27693133)This article highlights diagnosticdilemmas in the 2008 WHO classificationand the changes made in 2016 updateto resolve them. In MDS, dysplasiasand cytopenias in individual lineagesinvolved are not always concordant. The2016 classification uses general termMDS with single or multiple lineagedysplasias to create diagnostic categories.In addition, for higher risk MDS, thedisease with excess blasts is categorizedas MDSEB 1 or MDSEB 2.

2. Strupp C et al. New proposals of the WHOworking group (2016) for the diagnosis ofmyelodysplastic syndromes (MDS): char-acteristics of refined MDS types. LeuRes. 2017;57:78-84. (https:// www.ncbi.nlm.nih.gov/pubmed/28324772)A validation of the new 2016 WHOclassification of MDS was conducted withcentrally diagnosed 3528 patients in theDüsseldorf registry, showing MDS singlelineage dysplasia (MDS SLD) in 7.3%,multilineage dysplasia (MDS MLD) in27.7%, MDS RS SLD in 6.4%, MDS RS

MLD in 9.1%, Del(5q) in 4.5%, MDSwith excess blasts 1 (MDSEB 1) in 13.6%and MDSEB 2 in 17.6% patients. Theoverall survival and AML transformationwere also in line with the riskcategorization. When compared to WHO2008 classification, a major shift wasobserved in approx. 17% non-blasticpatients from RCMD (2008) to MDS RSMLD or MDS Del(5q) (2016). Survivalwas higher in SLD and Del(5q) patientsthan MLD or EB1/2 patients. For AMLprogression rate, as compared to SLD,MLD and del(5q) categories, EB1showed nearly 2x higher and EB2 had 3xhigher rates.

3. Xavier AC et al. Incidence and outcomesof paediatric myelodysplastic syndromein the United States. Br J Haematol.2017; Feb 27 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/28240841)The analysis of SEER database recordsbetween 2001 and 2011 revealed anincidence of pediatric MDS at 1.16cases/million population/year. Further-more, similar to adult MDS, the 5-yearsurvival of therapy-related pediatricMDS (41.2%) was significantly poorer ascompared to de novo pediatric MDS(71.3%, p=0.004).

TReATMeNT:Hypomethylating Agents:

1. Drusbosky L et al. Computational drugtreatment simulations on projections ofdysregulated protein networks derivedfrom the myelodysplastic mutanomematch clinical response in patients.Leuk Res. 2017;52:1-7. (https://www.ncbi. nlm.nih.gov/pubmed/27855285)Drug response was simulated forlenalidomide or hypomethylating agents(HMA) or for HMA+Lenalidomide.Using computational biology of genomicabnormalities in each patient intra-cellular pathway map was computed forindividual patients. The computational

model matched clinical responses in 80%MDS patients treated with lenalidomide(37/46) or HMAs (12/15) while thematching was 100% (10/10) in patientstreated with HMA + Lenalidomide.

ESAs and Growth Factors1. Park S et al. Outcome of lower-risk

patients with myelodysplastic syndromeswithout 5q deletion after failure oferythropoiesis-stimulating agents. J ClinOncol. 201, Mar 28 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/28350519)Using an international retrospectivecohort of 1698 patients with non-del(5q)lower risk MDS treated with ESA, theeffect of second line treatment subsequentto ESAs was assessed. The HI-E infrontline with ESA treatment was 61.5%with a median response duration of 17months. Patients without any response toESAs had a higher rate of AMLtransformation than those who initiallyresponded to ESA and then relapsed.Nearly 40% patients received second linetherapy after ESA failure includingHypomethylating agents, and lenalidomide,while approx. 60% patients received RBCtransfusion only. The HMA andLenalidomide treated patients had higherpropensity for AML transformation andlower 5year survival rates as comparedto those receiving transfusions only ortreatment with other agents.

2. Oliva EN et al. Eltrombopag versusplacebo for low-risk myelodysplasticsyndromes with thrombocytopenia(EQoL-MDS): phase 1 results of a singleblind, randomized controlled phase 2superiority trial. Lancet Haematol. 2017;4(3):e127-e136. (https://www.ncbi.nlm.nih.gov/pubmed/28162984)Eltrombopag (50mg to 300 mg) treatmentfor at least 24 weeks and until diseaseprogression versus placebo, showedplatelet response (HI-plt) in 47% (24/59)patients as compared to 3% of the total31 patients on placebo arm. Nearly 42%

MDS RESOURCESLITERATURE HIGHLIGHTS

higher risk myelodysplastic syndromes.Cancer. 2017;123(6):994-1002. (https://www.ncbi.nlm.nih.gov/pubmed/28094841)Int-2/high-risk MDS patients (n=102)were randomized 1:1 between azacitidine+ pracinostat vs azacitidine + placebo.Respectively in the two groups, the CRrate by cycle 6 was 18% vs 33%(p=0.07), median overall survival of 16and 19 months, and progression freesurvival of 11 and 9 months.

4. Welch JS et al. TP53 and decitabine inacute myeloid leukemia and myelo-dysplastic syndromes. N Engl J Med.2016;375(21):2023-2036. (https:// www.ncbi.nlm.nih.gov/pubmed/27959731)This single institution trial enrolled atotal of 116 subjects with AML or MDSwith 46% patients clearing marrow blaststo <5% level. The unfavorablecytogenetic profile patients had betterresponse (67%) with 20 mg/ m2 x 10 daysadministration of decitabine than thosewith intermediate or favorablecytogenetics (34%, p<0.001). Moreover,specifically in patients with TP53mutations the response was 100% (21/21patients) vs. 41% in wild type TP53patients (p<0.001).

5. Pappa V et al. A retrospective study ofazacitidine treatment in patients withintermediate-2 or high risk myelo-dysplastic syndromes in a real-worldclinical setting in Greece. Int J Hematol.2017;105(2):184-195. (https://www.ncbi.nlm.nih.gov/pubmed/27815858)A single country, multicenter, retro-spective chart review study (RETRO-AZA-MDS-001) conducted between Feb–Nov 2012 assessed clinical benefit/riskprofile of azacitidine in routine practicein int-2/high risk MDS. A total of 88patients with a median of 6.6 monthtreatment duration showed ORR- approx.38%, HI rate of 33%, AML transfor-mation in 6.8%, transfusion independencein 7.3% among transfusion-dependentpatients, and serious adverse events in

CD8+ with phytohemagglutinin asmeasured by CD69 expression, nearlydoubled after ESA treatment compared tonon-ESA treated patients.

Hypomethylating Agents:1. Zhang Z et al. Decitabine treatment

sensitizes tumor cells to T-cell mediatedcytotoxicity in patients with myelo-dysplastic syndromes. Am J Transl Res.2017;9(2):454-465. (https://www.ncbi.nlm.nih.gov/pubmed/28337274)Decitabine treatment of MDS-derivedcell lines significantly improved surfaceexpression of cancer-testis antigens(CTAs) and also led to incrementalrecognition of CTA expressing MDSderived cells by cytotoxic T cells. Therewas increased HLA and ICAM-1expression specific to cytotoxic T cells.These data may support a role ofdecitabine in active adaptive immunity inMDS.

2. Apuri S et al. Evidence for selectivebenefit of sequential treatment withhypomethylating agents in patientswith myelodysplastic syndrome. ClinLymphoma Myeloma Leuk. 2017 Jan 10[Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/28185797)A single institution study evaluatedeffectiveness of sequencing the twohypomethylating agents with each other.In the first line HI rates were comparablewith both agents 63% with Azacytidineand 50% with decitabine. In the secondline though, decitabine post azacitidineshowed 19% HI as the best responsecompared to 40% with azacitidine post-decitabine. In line with these results,AML transformation was lower with thelatter (29% vs 20% respectively). Themedian survival from the initiation ofsecond line however was comparable(17.8 mo vs 22 mo).

3. Garcia-Manero G et al. Phase 2,randomized, double-blind study ofpracinostat in combination withazacitidine in patients with untreated,

12

of the placebo patients had bleedingevents versus 14% with eltrombopagtreated patients (p=0.0025). The AMLtransformation and disease progressionrates were comparable in the two groups.

3. Garelius HK et al. Erythropoiesis-stimulating agents significantly delay theonset of a regular transfusion need innon-transfused patients with lower-riskmyelodysplastic syndrome. J Intern Med.2017;28(3):284-299. (https://www.ncbi.nlm.nih.gov/pubmed/27926979)The clinical impact of ESA use wasevaluated among 1696 subjectsregistered in EUMDS registry between2008 and 2014. Nearly 46% patientsreceived ESAs for a median duration of27.5 months. When compared with non-ESA patients, those treated with ESAsshowed a trend of survival benefit(HR=0.82, p=0.09) with the best resultsin patients not needing transfusions priorto ESA treatment. Among the latter groupof patients, post-ESA treatment, firsttransfusion was needed after a median of23.3 months (p<0.0001), while in thosewith prior transfusions, the time to post-ESA first transfusion was significantlyshorter (median 6.1 month). Additionally,the responding patients showedsignificantly lower risk of death(HR=0.065, p=0.018).

4. Deshet-Unger N et al. Erythropoietinadministration is associated withimproved T-cell properties in patientswith myelodysplastic syndromes. LeukRes. 2017;52:20-27 (https://www.ncbi.nlm.nih.gov/pubmed/27870945)In this study, MDS patients treated withESA were compared to non-ESA treatedMDS patients or healthy donors. Atbaseline, all MDS patients showedreduced number and function of CD4+ Tcells and elevated CD8+ T cellnumber/activity. Post ESA, the CD4+CD25+ cell counts were normalized inthe periphery. Also, in vitro activation ofboth T cell populations, CD4+ and

LITERATURE HIGHLIGHTS

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42%. Patients with no prior ESA werenearly 8 times more likely to achieve aclinical response with azacitidine(p=0.012).

IMiDs:1. Prebet T et al. Outcome of patients

treated for myelodysplastic syndromeswithout deletion 5q after failure oflenalidomide therapy. Oncotarget. 2017,Feb 8 [Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/28184031)An international retrospective studyassessed lenalidomide treated lower risknon-del(5q) MDS patients (n=384).Among these patients, 55% were treatedwith ESAs and 23% with hypomethylatingagents (HMA) before lenalidomidetreatment. The response to lenalidomidewas seen in 17% patients with amedianlenalidomide treatment duration of 15mo. Conversely, for the 64% who did notrespond to lenalidomide, the medianduration of treatment was only 4 mo.When HMA were used after lenalidomide,the overall survival was 51 mo vs. 31 mowith the best supportive care afterlenalidomide (p=0.01).

Allogeneic Bone Marrow Transplant:1. Martino R et al. Long-term follow-up of a

retrospective comparison of reduced-intensity conditioning and conventionalhigh-dose conditioning for allogeneictransplantation from matched relateddonors in myelodysplastic syndromes.Bone Marrow Transplant. 2017; Mar 20[Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/28319072)A multicenter retrospective studyinvolving 843 MDS patients receivedallogeneic marrow transplant from HLA-matched sibling donor. This study showedthat a 13 year relapse rate wassignificantly higher after reducedconditioning regimen (48%) vs standardmyeloablative regimen (31%, p=0.04),without any impact on overall survival.However, non-relapse mortality washigher in myeloablation group as

compared to reduced-intensity regimen(40% vs 31%, p=0.1).

RBC Transfusions:1. Lin Y et al. Prophylactic RhCE and Kell

antigen matching; impact on alloimmuni-zation in transfusion-dependent patientswith myelodysplastic syndromes. VoxSang. 2017;112(1):79-86. (https://www.ncbi.nlm.nih.gov/pubmed/28097704)A study of 176 transfusion dependentMDS patients reveals importance of aninstitutional policy for prophylacticantigen matching for RhCE and Kellantigens. Overall, 17% of the patientsdeveloped alloantibodies, with themajority showing at least one anti-RhCEor Kell antigens. When assessed for theprophylactic matching policy beforetransfusion, the rate was significantlylower (11%) vs. when no policy wasapplied (23%).

Novel Therapies:1. Wermke M et al. Mammalian-target of

rapamycin inhibition with temsirolimusin myelodysplastic syndromes (MDS)patients is associated with considerabletoxicity: results of the temsirolimus pilottrial by the german MDS study group(D-MDS). Br J Haematol. 2016;175(5):917-924. (https://www.ncbi.nlm.nih.gov/pubmed/27714772)A prospective study enrolled lower riskMDS patients with transfusion dependentanemia and/or neutropenia and higherrisk patients relapsed/refractory to 5-azacitidine. A total of 20 patients (9lower- and 11 higher-risk) were treatedwith a weekly 25mg dose of Temsirolimus.Only four patients showed stable diseasewithout HI after four months. Theremaining patients discontinued early dueto adverse events. A significant decline inmarrow vascularization was seen withtreatment without impact on the balanceof peripheral blood T-cell populations.

2. Swords RT et al. KB004, a first-in-classmonoclonal antibody targeting thereceptor tyrosine kinase EphA3 in

patients with advanced hematologicmalignancies: results from a phase 1study. Leuk Res. 2016;50:123-131. (https://www.ncbi.nlm.nih.gov/pubmed/?term=Sword+RT+and+EphA3)An anti-Ephrin receptor tyrosine kinasemonoclonal antibody was tested in aphase 1 study with multiple hematologicmalignancies including MDS and AML.The most common toxicities were grade1/2 infusion reactions in approx. 80%treated patients becoming dose limitingbeyond 250 mg. The weekly schedule ofthe drug was found to be well toleratedwith clinical responses noted in all thehematologic conditions tested.

PATHObIOlOgy:1. Hlaváčková A et al. Enhanced plasma

protein carbonylation in patients withmyelodysplastic syndromes. Free RadicBiol Med. 2017 Mar 12 [Epub ahead ofprint] (https://www.ncbi.nlm.nih.gov/pubmed/28300669)A total of 32 patients with MDS (RARS,RCMD, RAEB 1, or RAEB 2) wereexamined for protein carbonylation,indicative of reactive oxygen radicalactivity. These MDS patients and, inparticular, the RARS category, showedelevated protein carbonylation ascompared to healthy controls. Addition-ally, using tandem mass spectrometry, 27uniquely carbonylated proteins wereidentified in RARS patients, thepathobiologic significance of whichneeds further exploration.

2. Diamantopoulos P et al. Poly(ADP-ribose) polymerase-1 mRNA levelsstrongly correlate with the prognosis ofmyelodysplastic syndromes. BloodCancer J. 2017;7(2):e533. (https://www.ncbi.nlm.nih.gov/pubmed/28212373)

The median PARP1 mRNA levels correlatedwith advanced disease among WHO2008/2016 categories as well as amongIPSS/IPSS-R categories. Moreover, themedian overall survival and 5-yr survival

LITERATURE HIGHLIGHTS

14

rates were worse in patients with high vs.low PARP1 mRNA levels (OS- 37.4 mo vsnot reached, p=0.0001, and 29.8% vs88.9% respectively).

3. Makishima H et al. Dynamics of clonalevolution in myelodysplastic syndromes.Nat Genet. 2017;49(2):204-212. (https://www.ncbi.nlm.nih.gov/pubmed/27992414)Clonal dynamics were studied using wholeexome and/or targeted sequencing of 699patients (122/699 studied longi-tudinally).The number of mutations, their diversityand clone size increased at progression. Aset of mutations including FLT3, PTPN11,WT1, IDH1/2, NPM1 and N-RAS groupedas Type 1, were found to be newly acquiredat AML transformation, related to fasterprogression and poorer survival. On theother hand, another set of mutationsenriched in higher risk MDS like TP53,GATA2, KRAS, RUNX1, ASXL1, ZRSF2,STAG2, and TET2 (Type2) did not correlatewith AML progression or survival.

4. Westers TM et al. Immunophenotypicanalysis of erythroid dysplasia inmyelodysplastic syndromes. A reportfrom the IMDS Flow working group.Haematologica. 2017;102(2):308-319.(https://www.ncbi.nlm.nih.gov/pubmed/27758818)This multicenter study of the IMDS Flowworking group attempted to define flowparameters to distinguish MDS associateddyserythropoiesis from non-clonalcytopenias. In a multivariate analysis,expression of CD36 and CD71, intensityof CD71, and % CD117+ erythroidprogenitors best discriminated MDSfrom non-clonal cytopenias. The highspecificity (92%) of this marker set wasverified in a validation cohort.

5. Cremers EM et al. Implementation oferythroid lineage analysis by flowcytometry in diagnostic models formyelodysplastic syndromes. Haematologica.2017;102(2):320-326. (https://www.ncbi.nlm.nih.gov/pubmed/27658438)

The study analyzed 167 bone marrowaspirates (106 MDS and 61 cytopeniccontrols). The results showed acorrelation of the presence of erythroidaberrancies with MDS diagnosis and theaddition of erythroid aberrancies to twodifferent flow cytometric modelsincreased sensitivity of detecting MDS.

QuAlITy OF lIFe1. Luskin MR et al. Self-reported sleep

disturbance and survival in myelo-dysplastic syndromes. Br J Haematol.2017 Mar 8 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/28272741)In a single institution study with MDSpatients, using the “European organi-zation for research and treatment ofcancer quality of life questionnaire,”multivariable models showed that anemiaand sleep disturbance were bothassociated with fatigue (p<0.001).Additionally, sleep disturbance (p=0.002)and fatigue (p=0.04) were individualpredictors of overall survival.

ReVIeWS, PeRSPecTIVeS & guIDelINeSThe following articles provide significantreview of literature and/or innovativeperspective on the state-of-the-art in MDSor discuss therapeutic management guide-lines and identify need for additionalprospective studies.

1. Stahl M and Zeidan AM. Management oflower-risk myelodysplastic syndromeswithout del 5q; current approach andfuture trends. Exp Rev Hematol. 2017;10(4):345-364. (https://www.ncbi.nlm.nih.gov/pubmed/2827785)

2. Greenberg PL et al. Myelodysplasticsyndromes, version 2.2017, NCCNclinical practice guidelines in oncology.J Natl Compr Canc Netw. 2017;15(1):60-87. (https://www.ncbi.nlm.nih.gov/pubmed/28040720)

3. Almeida A et al. Recent advances in thetreatment of lower-risk non del(5q)myelodysplastic syndromes (MDS). LeukRes. 2017;52:50-57. (https://www.ncbi.nlm.nih.gov/pubmed/27883945)

4. Bejar R and Greenberg PL. The impact ofsomatic and germline mutations inmyelodysplastic syndromes and relateddisorders. J Natl Compr Canc Netw. 2017;15(1):131-135. (https://www.ncbi.nlm.nih.gov/pubmed/28040723)

5. Bejar R. Implications of moleculargenetic diversity in myelodysplasticsyndromes. Curr Opin Hematol. 2017;24(2):73-78. (https://www.ncbi.nlm. nih.gov/pubmed/27875374)

6. Wlodarski MW et al. Prevalence, clinicalcharacteristics, and prognosis of GATA2-related myelodysplastic syndromes inchildren and adolescents. Blood. 2016;127(11):1387-1397. (https://www.ncbi.nlm.nih.gov/pubmed/26702063)

We would like to thank

Suneel Mundle, a member

of the MDS Foundation,

and Rhea Mundle for

their assistance in

monitoring these

important peer-review

publications on MDS.

LITERATURE HIGHLIGHTS

15

TitleXxxx

A Photovoice approach was used – thepatients used cameras to capture images ofevents and experiences from their everydaylife that illustrated various perspectives onliving with the disease. Each patientcontributed approximately 25 pictures. Thepatients then told their stories associatedwith each picture in individual interviews.The interviews were tape recorded andtranscribed verbatim. Compiled narrativesfor each photo were then created by theresearchers and sent to the patients forvalidation.

All pictures, together with the narratives,were categorized in groups and subgroupsby the patients together with theresearchers in two consecutive half-daydialogue sessions to jointly identifycommon themes and sub-themes thatillustrated aspects of living with thedisease. Various strategies to cope with thedisease in everyday life were identified.The photographs and narratives werecategorized into six groups:

1. Being an individual person – morethan a diagnosis.

INTERNATIONAL MDS FOUNDATION NURSE LEADERSHIP BOARD

Erik Aerts, RNZürich, Switzerland

Angelika BitterStudy Coordinator/Nurse Dresden, Germany

Claudia Boglione, RNFlorence, Italy

Núria Borràs, RNBarcelona, Spain

Karen Campbell, RNEdinburgh, ScotlandUnited Kingdom

Hwang Chung Cheng JordanRN, MN, Adv DipSingapore

Nicole Crisp RN, BScN, MN, NP-adultEdmonton, Alberta, Canada

Erin Demakos, RN, CCRNNew York, New YorkUnited States

Rebecca Dring, RNMelbourne, Australia

Corien Eeltink, RN, MA ANPAmsterdam, The Netherlands

Lenn Fechter, RNStanford, CaliforniaUnited States

Janet Hayden, RN, BSc(hons), MPHLondon, United Kingdom

Miki Iizuka, RNTokyo, Japan

Jacqueline Jagger, BA, RNGosford, Australia

Christiane KahleLead Study Coordinator/Nurse Dresden, Germany

(Continued)

PhotoVoice for Patientswith MyelodysplasticSyndromes –Understanding thePatients’ StoriesPetra lindroos Kölqvist RN1, Hegegarelius MD1, Anna Ringheim QM2,Malin lindqvist RN1, Svante lifvergrenMD, PhD3

1Sahlgrenska University Hospital,Goteborg, Sweden; 2Regional CancerCentre West, Goteborg, Sweden; 3Centrefor Health Care Improvement, ChalmersUniversity of Technology, Sweden

Learning from patients’ experiences inorder to improve care services is a corefeature of the quality strategy at our clinic.MDS is a malignant disease that isassociated with anemia, increased risk ofinfections and bleeding tendency.Approximately 30% of the patients developacute myeloid leukemia. Getting amalignant diagnosis is always lifechanging and living with a serious illnesscan lead to increased anxiety and decreasedquality of life for the individual. Moststudies focus on medical aspects of thedisease. However, few qualitative studiesexplore patients’ experiences of living withMDS. The aim of the study was to learnhow MDS impacts patients’ daily lives,bringing their lived experiences in focususing ‘Photovoice’ — a participatoryresearch approach. The second aim was toexplore if the study could increase thepatient’s sense of empowerment.

Fourteen patients on active treatmentfor MDS at the hematology clinic atthe Sahlgrenska University Hospital,Goteborg, Sweden, were invited toparticipate in the study. Four patients (twowomen and two men) consented toparticipate, age 65–79 years. The patientshad had the diagnosis for more than 3months. The research team consisted of asenior consultant in hematology, tworegistered nurses specializing inhematology nursing working in the

outpatient clinic, one representative fromthe Regional Cancer Centre specializing inhealth care improvement, and the researchleader working at the Centre for HealthCare Improvement (CHI) at Chalmers. Thestudy was approved by the RegionalEthical Board in Goteborg.

The research group

16

Emily A. Knight, RN, BSN, OCNScottsdale, ArizonaUnited States

Sandra E. Kurtin RN, MS, AOCN, ANP-CTucson, ArizonaUnited States

Petra Lindroos Kolqvist, RNGoteborg, Sweden

Arno Mank, RN, PhDAmsterdam, The Netherlands

R. Denise McAllisterMS, ARNP, AOCNPClearwater, FloridaUnited States

Cindy Murray, RN, MN, NP-adultToronto, OntarioCanada

Geke Ong, RNLondon, United Kingdom

Phyllis Paterson RN, RSCN, Dip OncCambridge, United Kingdom

Jean A. RidgewayMSN,APN,NP-C,AOCNChicago, IllinoisUnited States

Barbara A. Rodgers, RN, BSN, OCNSeattle, WashingtonUnited States

Jayshree Shah APN-C, AOCNP, RN, MSN, BSN, BS, CCRPHackensack, New JerseyUnited States

Natalie Singer, MSc, RN, BSc(Hons) Glasgow, ScotlandUnited Kingdom

Samantha Soggee, RN, MNHeidelberg, Victoria, Australia

Mary L. Thomas, RN, MS, AOCNPalo Alto, CaliforniaUnited States

Sara M. Tinsley, PhD, ARNP, AOCNTampa, FloridaUnited States

Catherine Vassili, RNVictoria, Australia

2. Experiences of living with thedisease, e.g. anxiety, physical limitationsand the necessity of medications.

3. Experiences of meeting thehealthcare system. The healthcare systemis necessary for coping with the diseasewhile, at the same time, it disempowerspatients.

4. Different strategies for coping withthe disease, e.g. finding comfort in faith,obtaining knowledge about the disease.creating structures for reflection.

5. Strategies for wellbeing despite thedisease, e.g. being in nature, physicalexercise.

6. Living here and now, accepting thedisease.

During dialogue sessions, as well as inthe follow up interviews, the patientsexpressed feeling empowered by thismethod of processing the diagnosis ofMDS together with other patients.

The patients also expressed that sharingexperiences with others is a powerful wayto encourage empowerment – it expandsones own repertoire to handle everydayaspects of living with a malignant disease.

The combination of the patients’narratives and photos provides a richunderstanding of the patients’ experiencesliving with MDS. These narrativesemphasize the importance of having healthcare professionals taking the time to listento patient stories to learn about individualpatient experiences and perceptionsrelative to living with MDS. This studywas a participatory process in whichpatients and researchers worked side byside during the entire project. Ourexperience is that PhotoVoice is a valuableparticipative approach to capture patientexperiences. It might also be used withother patient groups, e.g. patients withimpaired cognitive function. The picturesand narratives are currently being used as avehicle to inspire improvement effortsfrom a patient’s perspective. The study hasbeen presented as a poster at theInternational Forum on Quality and Safetyin Health Care in Singapore 2016 and willbe presented at the Quality Fair in HealthCare in Goteborg 2017.

They are a part of the good things in life, so Ithink that I will show a picture of this, itmeans so much, for the wellbeing.

Life goes on out there anyway.It is a sign of loneliness which has been forcedupon you.

Music is positive, so of course, everythingthat is positive keeps one happy and cheerfuland able to enjoy life.

17

GLAM ASH 2016The Latin-American Group for

Myelodysplastic Syndromes (GLAM)meeting was held on the 4th of Decemberat the Manchester Hyatt Hotel in SanDiego. Authorities from Latin-AmericanHematology Societies, American Societyof Hematology, AA&MDS InternationalFoundation, the MDS InternationalFoundation and colleagues from Argentina,Brazil, Bolivia, Chile, Colombia, CostaRica, Ecuador, Guatemala, Peru, Paraguay,Uruguay and Venezuela attended thismeeting.

Main topics discussed:

MDS SurveyThis survey aims to collect epidemio-

logical and state-of-the-art diagnostic andtherapeutic tools in the region. This datawill be updated and published every twoyears. Results might be ready for the MDSFoundation’s International Symposium inValencia, May 2017.

a database with similar variables and acentralized coordination. An Argentineanplatform has been chosen.

Investigation and Clinical TrialsWe reconfirmed that GLAM is

determined to encourage investigation andhelp to promote clinical trials in MDSthroughout Latin America.

Patients, Relatives andHealthcaregivers Informationand Support

GLAM´s web page is underconstruction and will be a useful tool to

17

glAMcONTAcT INFORMATION

info@mds-la.oUruguayan Society of Hematology

(on behalf of GLAM)COLONIA 1086 OF.404

Montevideo, Uruguay

NEWS FROM AROUND THE WORLD

Training and TeachingOne of the most important projects of

GLAM is to organize scientific MDSmeetings, workshops, symposiums, etc.in different Latin American countries.Colleagues from Mexico have shown atrailer from Chiapas City, a beautifulplace where the 6th Latin AmericanMDS Symposium is going to be celebratedin 2018.

MDS Latin-American CommonRegistry

It is extremely necessary to develop aLatin American online common MDSRegistry. All the attendants agreed to share

help Latin American groups of MDSpatients, relatives and healthcaregivers.

lATIN-AMeRIcAN gROuP FORMyelODySPlASTIc SyNDROMeSThe Latin-American Group for

Myelodysplastic Syndromes (GLAM) is amulti-disciplinary group integrated byhealth professionals from Argentina,Bolivia, Brazil, Chile, Colombia, CostaRica, Dominican Republic, Ecuador, ElSalvador, Guatemala, Honduras, Mexico,Panama, Paraguay, Peru, Uruguay andVenezuela, with a common aim: study MDSfrom pathogenesis through clinical andtherapeutic approaches.

FROM THE FOUNDATION

NEWS FROM AROUND THE WORLD

18

In honor ofMDS WORLD

AWARNESS DAY,our Center of Excellencein Shanghai, China,

The Sixth Hospital Affiliatedto Shanghai JiaotongUniversity, held lecturesfor both healthcareprofessionals and patients withtheir families.

19

MDS IN FOCUS

MDS Remains anIncurable Disease Forthe Majority of PatientsMyelodysplastic Syndromes in Focus on World MDSAwareness Day

Sandra Kurtin, RN, MS, AOcN, ANP-c, PhDcNurse PractitionerThe University of Arizona Cancer CenterTracey IracaMDS Foundation, Inc.

Myelodysplastic syndromes (MDS)represent a group of rare bone marrowfailure cancers most common in the olderadult population, with a median age ofonset of 73 years. Healthy bone marrowproduces immature blood cells — calledstem cells, progenitor cells or blasts — thatnormally develop into mature, fullyfunctional red blood cells, white blood cellsand platelets. In MDS, these stem cells maynot mature and may accumulate in the bonemarrow or they may have a shortenedlifespan, resulting in fewer than normalmature blood cells in the circulation. Lowblood cell counts are a hallmark feature ofMDS and are responsible for some of thesymptoms that MDS patients experience —infection, anemia, spontaneous bleeding oreasy bruising.

MDS remains an incurable disease inthe absence of an allogeneic bone marrowtransplant, which is not an option for themajority of MDS patients due to their age,having other illnesses and/or not having acaregiver that is able to provide complexcare daily for several months following thetransplant. There are only three FDA-approved disease-modifying agents for thetreatment of these diseases, all of thesebeing developed through clinical trials.Unfortunately, the estimated clinical trialsenrollment in the United States for cancer

patients is approximately 4 percent of thetotal cancer patient population. Whenconsidering the older adult and rarediseases such as MDS, this number isestimated to drop below 2.5 percent.

In addition, the majority of health careis provided in the outpatient setting withonly brief episodes of health care providerinteraction. Caregivers, including partners/spouses, other family members and friends,are expected to assume a primary role in

MDS IN FOCUS

providing medical and personal care andsupport of the patient with little or noformal training. Many patients andcaregivers may be overwhelmed and are atincreased risk for anxiety, depression,fatigue and other physical andpsychological distress. The MDSFoundation, Inc. works to provide hopewith innovation in science, advocacy andmost importantly support of patients andcaregivers living with MDS.

SEARCH OPEN STUDIES AT THE MDS FOUNDATIONClinical trials are a final and crucial step on the path todeveloping better treatments for patients…and we now havethe opportunity to participate in more clinical trials than ever,specifically for MDS.

Historically, 85% of all clinical trials face delays and 30% never get off the groundbecause of lack of volunteers.

The good news is that you now have the power to propel clinical research towardsbreakthroughs that MDS patients can feel in their everyday lives.

Learn which studies are currently seeking participants at www.mds-foundation.org/clinical-trial-announcements.

SEARCH A NATIONAL REGISTRY OF CLINICAL TRIALSSearch the NIH registry of MDS clinical trials underway in the United States and beyondat www.clinicaltrials.gov.

ASK ME

about

CLINICALTRIALS

HOW TO FIND OPEN MDS CLINICAL TRIALS

20

Qualifying for aCompassionateAllowance with MDS

Thankfully, for those diagnosed withMDS, Social Security disability benefitsare an option. Both Social SecurityDisability Insurance (SSDI) andSupplemental Security Income (SSI)were created to help people in need andcan provide financial assistance to thosewith disabling conditions. In some severecases, MDS can even qualify for aCompassionate Allowance, meaningyour claim could be approved in as littleas 10 days.

Qualifying for DisabilityFirst, it is important to understand what

qualifies for disability benefits. Whenreviewing applications, the first thing aSocial Security agent looks to is yourdiagnosis. Diagnoses are evaluated usingthe “Blue Book” — a list of all disabilitiesapproved by the Social SecurityAdministration (SSA). Those with MDSqualify under Section 7.10 of the BlueBook: “Disorders of bone marrow failure.”If you can show evidence of their MDSdiagnosis as well as records of threehospital visits within a year due to yourillness, or blood transfusions every 6 weeksor more, then the SSA will consider you“disabled” and medically eligible forbenefits.

The other factor when determiningeligibility is income and past work history.These will determine if you technicallyqualify for benefits, as well as what type ofbenefits you qualify for. To receive SSDI,an applicant must have contributed acertain amount of money (called “workcredits”) to the Social Security system intheir working years. The older an applicantis, the more credits they must havecontributed in order to qualify. The goodnews is that the vast majority of applicantswho had just part-time jobs will qualify forSSDI benefits.

If an applicant has not contributedenough credits or is unemployed (a stay-at-home mom, for example), he or she mayqualify for SSI instead. Qualification for SSIis based strictly on income — if you aredeemed disabled and do not earn more thanthe monthly cut-off, then you are eligible forSSI benefits. Because SSI is needs based,you will not be approved if you have aspouse who’s earning a decent wage.

Qualifying for a CompassionateAllowance

MDS can be an incredibly limitingdisorder, causing extreme physical,mental, and financial strain for thoseaffected. Because of its severity, peoplecan occasionally qualify for aCompassionate Allowance during theirdisability application.

Compassionate Allowances areexpedited processes that provide financialbenefits to applicants far sooner than othernormal disability applicants. Terminalcancers and severe genetic disorders oftenqualify because of the time constraintstheir severe impairments present. MDS isconsidered a type of severe bone and bloodcancer, so applicants in late stages of thedisorder are often candidates for theprogram. While payments still takeanywhere from a few weeks to a fewmonths to be dispersed, the approval ismuch quicker than the traditional 6–12+month decision period.

To qualify for the CompassionateAllowance, your MDS must be severeenough to require a bone marrowtransplant. After the transplant, you willautomatically medically qualify for SocialSecurity benefits for 12 months. After 12

months, the SSA will revaluate your claimto determine if you are still medicallyeligible for benefits.

It is important to note that Compassion-ate Allowance recipients do not receiveMedicare faster than normal. Just as withother disability applicants, Medicare isusually awarded 24 months after thedisability onset date. If CompassionateAllowance financial benefits are still notenough to cover the medical/financial strainof MDS, it is important to seek otherinsurance options during this waiting period.

Applying for Benefits Applications for SSDI can be found on

the SSA’s main website. FAQs and otherimportant information can also be foundhere if you have any questions about theapplication or the process. Applications canalso be filed in person at your local SocialSecurity office.

Applications for SSI are currentlyunavailable online. However, it isrecommended that the Online Applicationfor Disability Benefits be filled out prior toapplying for benefits. While this isn’t theofficial application, the informationprovided can be transferred to yourapplication and helps to start the disabilityprocess. An appointment can then be madeto fill out an application by calling yourSocial Security office.

When applying, be sure to submit asmuch information as possible: How yourMDS keeps you from working, the namesand locations of every doctor who hastreated you, and your response to anytreatment. The more medical evidenceyou have on your side, the more likely youare to be approved for disability benefitswith MDS.

This article was provided by DisabilityBenefits Help, an independent organi-zation dedicated to helping people receivethe Social Security disability benefits theyneed. If you would lke to know moreabout qualifying for disability benefitswith MDS, email help@disability-benefits-help.org.

SOCIAL SECURITY AND MDS

Thankfully, for those

diagnosed with MDS,

Social Security disability

benefits are an option.

2014 RARE DISEASE DAY

21

2014 RARE DISEASE DAYSPREADING THE NEWS WORLDWIDE

2014 RARE DISEASE DAY

2014 RARE DISEASE DAY

May 20chicago, Il

MARK YOUR CALENDAR FOR THE LOCATION NEAREST YOU!PLANNED FUTURE MDS FORUM EVENTS FOR 2017

Don’t miss out on these informative, FREE events.

May 20Seattle, WA

October 28in honor of MDS World

Awareness DaySan Francisco, cA

November 18Iowa city, IA

May 5Valencia, Spain

MIDWEST/WEST

SOUTH

Register TodayFOR OUR FREE EVENTS

MIDWEST

INTERNATIONALOctober 28in honor of MDS World Awareness Day

Atlanta, gA

November 18San Antonio, TX

LEARN MORE AT:www.mds-foundation.org/patient-and-family-forums/

Many patients and caregivers have never met another person diagnosed with MDS until they connect with them at one ofour forums. If you’ve never attended one before, you won’t want to miss this opportunity to meet others and to learn more

about MDS, current treatments, and emerging therapies from leading experts. Not only will you find answers,support and hope for MDS, but you will learn tips and strategies for patients and caregivers lIVINg with MDS.

June17Middletown, NJ

September 9buffalo, Ny

MIDATLANTIC

PATIENTS & CAREGIVERS LIVING WITH MDS FORUMS

22

Today, 238 people were told that they have MDS-worldwide. The MDS Foundation, Inc. is working hard to change this reality and we ask for yourmembership support in our global efforts to change the outcomes of MDS.

WHAT ARE YOUR 2017 MDS MEMBERSHIP BENEFITS?� You are part of the solution to change MDS outcomes. Your membership fee helps support global physician and patient educational

initiatives, and helps to empower patients with courage and hope.� You will receive two printed issues of The MDS-News, which includes the latest on MDS as well as exceptional patient and caregiver stories.� You are updated regularly on the status of our Global Centers of Excellence and their patient events that encourage collaboration.� You are provided information on the latest clinical trials to potentially share or participate in.� You gain access to MDS awareness materials to share with family and friends.� You are given the opportunity to participate in or host support group events with your friends & community.

HOW DOES YOUR MEMBERSHIP HELP?� Your membership supports over 1,000 educational packets to families and caregivers free of charge annually, to help navigate through their

MDS diagnosis.� Your membership helps our Patient Liaison respond to over 1,300 on-line requests annually.� Your membership supports over 170 Centers of Excellence worldwide. We believe this is imperative as these centers serve as our patient

referral base, and this partnership helps the MDS community collaborate and engage in innovative practices in the diagnosis and care of MDSpatients.

� Your membership helps to distribute over 8,000 translated pieces of MDS materials annually.� Your membership enables MDSF to support approximately 250 professionals collaborating through International Working Groups – with

researchers in 37 countries, and on 6 of the 7 continents.� Your membership helps to educate patients, caregivers and professionals at live events. This year MDSF will host our International Symposia

in Valencia, Spain. We anticipate 1,500 professionals in attendance. We will also host 11 live patient events.� Your support in 2017 will help the MDS Foundation develop the growth of our Pediatric Centers of Excellence program to support children

and their families who are living with MDS.

MDS PATIENT AND PROFESSIONAL MEMBERSHIPMEMBERSHIP OPPORTUNITY

“When the MDS diagnosis first came, I had nothing.

I had no information and no support. Once I

connected with MDSF, I soon had lots of

knowledge, understanding, and caring support.”

Although most cases of MDS are found after

the age of 50, MDS can occur at any age.

In children, about 30 percent of MDS

progresses to acute myeloid leukemia (AML).

We believe that through greater collaboration,

science will change these outcomes.

23

MEMBERSHIP OPPORTUNITY

2017 MDS PATIENT MEMBERSHIP OPTIONS

$35 Community Membership (includes benefits listed above)

$70 Sharing Hope Membership (includes benefits listed above as well as a membership scholarship for a patient or caregiver in need)

$250 Changing the Future of MDS Membership (includes benefits listed above as well as additional support for the MDSFoundation as we work together to change the future of MDS) Member names are listed on the MDSF website.

2017 MDS PROFESSIONAL MEMBERSHIP OPTIONS$50 Community Professional Membership – (includes discounted registration rates at MDSF meetings, discounted subscription

rates to Leukemia Research, as well as access to MDSF resources for distribution to your patients)

$250 Changing the Future of MDS Professional Membership (includes discounted registration rates at MDSF meetings,discounted subscription rates to Leukemia Research, access to MDSF resources for distribution to your patients, as wellas the opportunity to present at MDSF patient events in your region. In addition, $50 of your membership will helpsupport a Professional outside of the United States that represents a CoE in financial need. Member names are listedon the MDSF website.

TOGETHER WE ARE A COMMUNITY RESOURCE OF HOPE FOR THOSE LIVING WITH MDS

Founded in 1994, the US-based MDS Foundation is the only not-for-profit international organization dedicated solely to MDS. Worldwide,87,000 cases are diagnosed each year and our mission is to serve MDS patients to ease the burden of this terrible disease and ultimatelychange MDS outcomes. Over the last 20 years, the treatment and understanding of MDS has evolved in many ways. Once referred to aspre-leukemia, MDS is now recognized worldwide as a blood cancer. Originally, there were no official treatments for MDS. Today, there are3 approved treatment options with many more in the development phase.

OUR MISSION: The MDS Foundation, Inc., is an international organization devoted to the support and education of patients andhealthcare providers with innovative research into the fields of MDS and related myeloid neoplasms in order to accelerate progressleading to the control and cure of the myelodysplastic syndromes.

OUR VISION: By building an international community of physicians, researchers, and patients, we will make potential curative therapiesaccessible to all patients with MDS.

TO BECOME A MEMBER VISIT: https://www.mds-foundation.org/membership

The MDS Foundation, Inc.4573 South Broad Street, Suite 150, Yardville, NJ 08620

800-637-0839/609-298-1600

The MDS Foundation, Inc. is a 501c3 tax exempt organization.

2424

Thinking of joining the MDS Foundation as a Professional Member? To join the MDS Foundation and help us fulfill our mission of moving closer to a cure for MDS, please visit our website at

http://www.mds-foundation.org/professional-annual-membership-application.

CURRENT MEMBERS:

Camille Abboud, MDSophia Adamia, PhDCalum Adams, ANPAref Al-Kali, MDSteven L. Allen, MD,Hanan Alwazzan, MDErica Andersen, MDMartha Arellano, MDChristopher Arthur, MDAnita Atema, MScMaria R. Baer, MDGabriela Baerlocher, MDHaiyan Bao, MDAsad Bashey, MDMarielle Beckers, MDKatharine Bee, PhDRafael Bejar, MD, PhDMonika Belicková, MDJohn M. Bennett, MDHarriet A. Bering, MDMassimo Bernardi, MDEmmanuel C. Besa, MDLeigh-Anne BlairNicolas Bonadies, MDAdam Boruchov, MDDominique Bordessoule, MDMichael Boxer, MDDavid T. Bowen, MDRaul C. Braylan, MDRandy A. Brown, MDAndrew M. Brunner, MDRena Buckstein, MD, FRCPCGesine Bug, MDThomas W. Butler, MDHuojun Cao, MDJheremy Enrique Reyes Castellanos, MDHugo Castro-Malaspina, MDJaroslav Čermák, MD, PhDMustafa Cetiner, MDVictor Chang, MD, FACPLynette Chee, MDLimei Chen, MDQiusheng Chen, MDSuning Chen, MD, PhDJason X. Cheng, MD, PhDJune-Won Cheong, MD

Laura Yolanda Chialanza Garcia, MDShigeru Chiba, MDJonathan K. Cho, MDGrace Christou, MDStephen Chung, MDChristopher R. Cogle, MDRobert H. Collins, Jr., MD, FACPSeth J. Corey, MDRachel Cotter, RNLarry Cripe, MDGerard Crotty, MDGuiyun Cui, MDPeter T. Curtin, MDLucy CussansMagdalena Czader, MD, PhDCarlos M. de Castro, MDFabio Pires De Souza Santos, MDTheo J.M. de Witte, MD, PhDConsuelo del Cañizo, MD, PhDH. Joachim Deeg, MDMichel Delforge, MD, PhDMatteo G. Della Porta, MDMike Dennis, MDAmy E. DeZern, MD, MHSBruce Dezube, MDRishi Dhawan, MDJohn F. DiPersio, MD, PhDMinghui Duan, MDTheofanis Economopoulos, MDM. Tarek Elghetany, MDSarah England, PA-CDouglas V. Faller, MD, PhDSalman Fazal, MDLenn Fechter, RN, BSNDonald I. Feinstein, MD, MACPSandor Fekete, MDJosè Maria Ferro, MDMaria E. Figueroa, MDKalman Filanovsky, MDChun Yew Fong, MDJames M. Foran, MD, FRCPHeiner Frost, MDSteven Fruchtman, MDArnold Ganser, MDAlejandro Garcia-Hernandez, MDGuillermo Garcia-Manero, MD

Michelle Geddes, MDAaron T. Gerds, MD, MSUlrich Germing, MDGudrun Goehring, MDStuart L. Goldberg, MDCarlos Vigil Gonzales, MDSteven D. Gore, MDKatharina Götze, MDMarie Pierre Gourin, MDTimothy Graubert, MDUri Greenbaum, MDPeter L. Greenberg, MDElizabeth A. Griffiths, MDGeorge Grigoriadis, MDKirsten Grønbaek, MDEmmanuel Gyan, MD, PhDDetlef Haase, MD, PhDTorsten Haferlach, MDStephanie Halene, MDAmr Hanbali, MDCurtis A. Hanson, MDRobert P. Hasserjian, MDRobert Hast, MDBrenda HawkesGuangsheng He, MDStefan Heinrichs, PhDEva Hellström-Lindberg, MD, PhDCharles Hesdorffer, MDAndreas Himmelmann, MDMichel Hoessly, MDInga Hofmann, MD,Gang Huang, PhDSang Mee Hwang, PHDIshmael Jaiyesimi, DOPeng Ji, MDBrian A. Jonas, MD, PhDMark Juckett, MDHagop M. Kantarjian, MDAly Karsan, MDSuresh B. Katakkar, MD, FRCPCJonathan Kell, MDPeter Keller, MDMelita Kenealy, MDMichael Kenneth Keng, MDWolfgang Kern, MDLeslie Kerns, RN

2014 RARE DISEASE DAYJOIN THE MDS FOUNDATION

25

Samer Khaled, MDSally Killick, MDLars Kjeldsen, MD, PhDJeffery Klco, MDVirginia M. Klimek, MDH. Phillip Koeffler, MDRami Komrokji, MDJanusz Krawczyk, MDRavi Krishnadasan, MD, FACPNicolaus Kröger, MD, PhDRajat Kumar, MDYueyun Lai, MDWendy Lam, MDSaskia Langemeijer, MDAmelia Langston, MDRichard A. Larson, MDClaudio Marcelo Lastrebner, MDLaszlo Leb, MDJohanna B. Leonowicz, MDBing Li, MDXiao Li, MD, PhDJane L. Liesveld, MDAlan F. List, MDMark R. Litzow, MDJohannes Loferer, MDSelina Luger, MDRoger M. Lyons, MDAlan MacWhannell, MDUlrich Mahlknecht, MD, PhDInga Mandac Rogulj, MDLori Maness, MDGabriel N. Mannis, MDMarkus G. Manz, MDKatherine Marsden, MDYvonne Matienko, LPNAkira Matsuda, MDPhilip L. McCarthy, MDRichard McMasters, MDZoe McQuilten, MDStephen Medlin, MDKenneth R. Meehan, MDRaul R. Mena, MDDrorit Grizim Merkel, MDWolfgang Meyer, MDKen Mills, MDMoshe Mittelman, MDYasushi Miyazaki, MDSanjay Mohan, MDJoseph O. Moore, MDAlvaro Moreno-Aspitia, MDLynn Moscinski, MDGhulam J. Mufti, DM, FRCP, FRCPath

Suneel D. Mundle, PhDTracy Murphy, MDHan Myint, MD, PhDAbdulqadir NashwanPhuong L. Nguyen, MDCharlotte Niemeyer, MDStephen D. Nimer, MDBenet Nomdedeu, MDNicolas Novitzky, MDNolyn Nyatanga, MDCasey L. O’Connell, MDMargaret O’Donnell, MDKiyoyuki Ogata, MD, FACPSeishi Ogawa, MDKazuma Ohyashiki, MD, PhDStephen Opat, MDHoward S. Oster, MD, PhDRose Ann Padua, PhDVassiliki Pappa, MDStefani Parmentier, MDJakob R. Passweg, MDMichael Petrone, MDMichael Pfeilstöcker, MDUwe Platzbecker, MDVicki Plumb, RNDaniel Pollyea, MD, MSJulio Pose Cabarcos, MDBayard L. Powell, MDGabrielle T. Prince, MDJun Qian, MDBruno Quesnel, MDTomas Radivoyevitch, PhDFernando Ramos, MD, PhD, MPHMichael Rauh, MDAzra Raza, MDShannon Reilly, NPGail Roboz, MDElvira Rodrigues Pereira Velloso MD, PhDChristian Rose, MDAlicia Rovo, MDNitzan SagyGrazia Sanpaolo, MDMichael R. Savona, MD, FACPHamid Sayar, MD, MSAleksandar Savic, MDMary Lynn Savoie, MDGary J. Schiller, MDJason R. Schwartz, MDKaren Seiter, MDDominik Selleslag, MDJohn F. Seymour, MDRichard K. Shadduck, MD

Jamile M. Shammo, MDLee-Yung Shih, MDJake Shortt, MDLewis R. Silverman, MDBarry S. Skikne, MDScott E. Smith, MD, PhD, FACPQiang Song, MDYuanbin Song, MDEduardo Sotomayor, MDMichail Spanoudakis, MD, PhDKellie Sprague, MDLisa Sproat, MDAspasia Stamatoullas, MDMargarete Stampfl-Mattersberger, MDHarry Staszewski, MDReinhard Stauder, MDDavid P. Steensma, MDGalia Stemer, MDJohn Storring, MDArgiris S. Symeonidis, MDAkifumi Takaori, MDGevorg Tamamyan, MDJames E. Thompson, MDRaoul Tibes, MDHwei-Fiang Tien, MDMasao Tomonaga, MDHongyan Tong, MDZuzana Tothova, MD, PhDArjan van de Loosdrecht, MD, PhDAmit Verma, MDCarolina Villegas Da Ros, MDAthina Nora Viniou, MDAlison R. Walker, MDXiaomin Wang, MDXin Wang, MDZhen Wang, MDRichard A. Wells, MDJohn P. Whitecar, Jr., MDGail Wilmot, RNStefan Wirths, MDLeah Wolfe, R.Ph.Anthony Woods, MDDepei Wu, MDZhijian Xiao, MDYumi Yamamoto, BAKaren Yee, MDCecilia Arana Yi, MDYataro Yoshida, MDJ. Dudley Youman, MDLinda Young, RNWenjuan Yu, MDLing Zhang, MDNancy Zhu, MD

2014 RARE DISEASE DAYJOIN THE MDS FOUNDATION

26

With your help, the cure is within reach!

I want to make a difference...

Be A Champion of HopeYour donation makes a difference!

statement of purposeThe Myelodysplastic Syndromes Foundation, established by an international group of physicians and researchers, is a nonprofit healthorganization devoted to serving those patients afflicted with MDS. Until the Foundation was set up, no formal organization had beendevoted to MDS.

the foundation’s missionThe MDS Foundation, Inc. (MDSF) is an international organization devoted to the support and education of patients and healthcareproviders with innovative research in the fields of MDS and related myeloid neoplasms in order to accelerate progress leading to thecontrol and cure of these diseases. By building an international community of physicians, researchers, and patients, we will makepotentially curative therapies available for all patients with MDS.

contact usPhone within in the US: 1-800-MDS-0839Outside the US only: 1-609-298-1035Fax: 1-609-298-0590E-mail: patientliaison@mds-foundation.org

by making a tax-deductible contribution of

� $35 � $55 � $100 � $250 � $500 � $1000 � Other $_______

Name

Address

City/State/Zip

Email

Please make all checks payable to the MDS Foundation.

� Mastercard � Visa � American Express

Card No. Exp Security Code

Mail to: The MDS Foundation, Inc., 4573 South Broad St., Suite 150, Yardville, NJ 08620All contributions are tax-deductible.

the myelodysplastic syndromes foundation

To learn about MDS visit us at

www.mds-foundation.org

The MDS Foundation, Inc.4573 South Broad StreetSuite 150Yardville, NJ 08620

2727

TESTIMONIALS

“Thank you for providing a bookletthat addresses many of my questionsand provides resources to seekanswers to other questions.”Lindsay G.

“This information was very helpful tohelp me understand all about MDS. Iwant to share a copy with a friend.”

Anna A.

“The online book is very helpful.Would be very happy to have thehardcopy for my family.”Debbie L.

“Great association!”Selemon G.

“Thank you for making these booksavailable. They're the most accessibleI've found so far.”Maya T.

“My father was diagnosed withMDS in Oct 2016 and this is thebest site I have found online” I would love to provide him withthese books of information aboutMDS. Thank you. Rebecca V.

“My parents being techno-logically challenged, these bookswould be a great resource in this,the beginning of our education.Thank you for aiding us in thistime of need. Let the battle begin!”Tracey A.

The Building Blocks of Hope Handbookprovides strategies for patients andcaregivers living with MDS. This program isdesigned to give patients and caregivers thein depth information that they are lookingfor and to allow them to take an active partin their MDS journey. The BBoH isavailable in several languages. call 1-800-MDS-0839 for your FRee copy today.

Pierre Fenaux, MDHôpital St Louis, Université Paris 7

Peter L. Greenberg, MDStanford University School of Medicine

Sandra E. Kurtin, RN, MS, AOCN, ANP-CThe University of Arizona Cancer Center

Alan F. List, MDMoffitt Cancer Center

Luca Malcovati, MDUniversity of Pavia School of Medicine

Stephen D. Nimer, MD, ChairmanSylvester Comprehensive Cancer Center

MEMBERS EMERITUS

John M. Bennett, MDRochester, New York, USA

Charlotte M. Niemeyer, MDFreiburg, Germany

Franz Schmalzl, MDInnsbruck, Austria

BOARD OF DIRECTORS

OFFICERS

Susan Hogan, Operating Director

Tracey Iraca, Secretary

Roberta Smith, CPA, Treasurer

Stuart Goldberg, MD

Jennifer Keam, MD

Deborah Peirce

Julia McGuire, Advisor

DEVELOPMENT BOARD

Rafael Bejar, MD, PhDMoores Cancer Center at theUniversity of California, San Diego

Rena Buckstein, MD, FRCPCSunnybrook Health Sciences Centre

Mario Cazzola, MD, ChairmanUniversity of Pavia School of MedicineFondazione IRCCS Policlinico San Matteo

Theo J.M. de Witte, MD, PhDRadboud University Nijmegen Medical CentreNijmegen Centre of Molecular Life Sciences

Erin P. Demakos, RN, CCRNIcahn School of Medicine at Mount Sinai

Benjamin Ebert, MD, PhDDana-Farber Cancer Institute

Silvia M. M. Magalhães, MD, PhDFederal University of CearáHospital Universitário Walter Cantídio

Uwe Platzbecker, MDUniversitätsklinikum Carl Gustav Carus

Yasushi Miyazaki, MDNagasaki University

Ghulam J. Mufti, DM, FRCP, FRCPathKing’s College London & King’s College Hospital

Akiko Shimamura, MD, PhDDana-Farber Cancer Institute

Lewis R. Silverman, MDIcahn School of Medicine at Mount Sinai

MEDICAL & SCIENTIFIC ADVISORY BOARD

28

Not too many people can say this, but breast cancer saved my life.

JANE MASSEY, MDS PATIENT, SPEAKS:

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29

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30

Syros AnnouncesApproval ofInvestigational DeviceExemption (IDE) forBlood Test to IdentifyCancer Patients withProprietary BiomarkersIDE Allows Syros to Expand OngoingPhase 2 Clinical Trial of SY-1425 intoNewly Diagnosed Acute MyeloidLeukemia and Low-Risk MyelodysplasticSyndrome Patients

cAMbRIDge, MassacusettsOctober 11, 2016 – Syros Pharmaceuticals(NASDAQ: SYRS) today announced thatthe U.S. Food and Drug Administration(FDA) has approved an investigationaldevice exemption (IDE) for a laboratory-based blood test to detect proprietarybiomarkers discovered using theCompany’s gene control platform to selectpatients for enrollment in the ongoingPhase 2 clinical trial of Syros’ lead drugcandidate, SY-1425, a selective retinoicacid receptor alpha (RARα) agonist.

The approval of the IDE allows Syrosto expand its Phase 2 clinical trial toinclude newly diagnosed acute myeloidleukemia (AML) patients 60 years of ageor older who are not suitable candidatesfor standard chemotherapy and low-risktransfusion-dependent myelodysplasticsyndrome (MDS) patients who testpositive for the biomarkers. The trial iscurrently enrolling genomically definedpatients with relapsed or refractory AMLor high-risk MDS identified using thebiomarker test.

“The approval of the IDE is animportant milestone in the development ofSY-1425 because it allows us to expandinto a broader set of AML and MDSpatients and potentially benefit four patientpopulations with high unmet medicalneed," said Nancy Simonian, MD, Syros’

Chief Executive Officer. “This achieve-ment is a testament to our ability todiscover genomically defined subsets ofpatients who are most likely to respond toour gene control therapies and collaboratewith partners to develop biomarker tests toidentify these patient subsets, which is akey part of our strategy to advance a newwave of gene control medicines.”

Using its gene control platform, Syrosdiscovered subsets of AML and MDSpatients whose tumors have a highlyspecialized regulatory region of non-coding DNA, known as a super-enhancer,that is associated with the RARA gene,which codes for the RARα transcriptionfactor. The super-enhancer is believed tolead to over-production of the RARαtranscription factor, locking cells in animmature, undifferentiated and proliferativestate. Syros further investigated thisbiology directly in patient tissues andconducted preclinical studies showing thatthe RARA super-enhancer is predictive ofresponse to treatment with SY-1425 inmodels of AML. Based on those data,Syros developed a biomarker strategy forits Phase 2 trial to identify these subsets ofAML and MDS patients it believes aremost likely to respond to treatment withSY-1425. Syros estimates that approxi-

mately 25 percent of AML and MDSpatients have the RARA super-enhancer.

The proprietary biomarkers weredeveloped into a validated laboratory testin collaboration with a diagnosticscompany under Clinical LaboratoryImprovement Amendment, or CLIA,guidelines using a well-establisheddiagnostic platform. The test is currentlybeing used to select relapsed or refractoryAML or high-risk MDS patients in theongoing Phase 2 trial of SY-1425. Thediagnostics company submitted the IDE tothe FDA, which was required forprospective selection of patients withnewly diagnosed AML and low-risktransfusion-dependent MDS for the trial.

The Phase 2 clinical trial of SY-1425 isa multi-center, open-label trial exploringsafety and efficacy. The primary endpointis overall response rate for AML andhigh-risk MDS patients and red bloodcell transfusion-independence rate forlow-risk MDS patients. Other endpointsinclude assessment of pharmaco-dynamic biomarkers, duration of response,safety and tolerability, and overall andprogression-free survival.

Additional details about the trial can befound using the identifier NCT02807558 atwww.clinicaltrials.gov.

PRESS RELEASE

AML CORNER

31

To all the patients participating in clinical trials and to the families, nurses and physicians who support them, we thank you.For you and with you, we are committed to improving the lives of people with MDS, AML and other serious diseases by developing medicines that control the expression of disease-driving genes.

To learn more about our Phase 2 clinical trial in MDS, please visit clinicaltrials.gov and search by the trial identification number NCT02807558.

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33

� An established university (or equivalent) program

� Recognized morphologic expertise in MDS

To be recognized as a center of excellence, an institution must have the following:

university of Southern californiaKeck School of MedicineLos Angeles, CaliforniaCasey L. O’Connell, MD

COLORADOuniversity of coloradoSchool of Medicineuniversity of colorado cancer centerAurora, ColoradoDaniel Aaron Pollyea, MD, MS

CONNECTICUTyale cancer center/Smilow cancer Hospitalyale univesity School of MedicineNew Haven, ConnecticutSteven D. Gore, MD

FLORIDAAll children’s HospitalSt. Petersburg, FloridaGregory Hale, MDMayo clinicJacksonville, FloridaJames M. Foran, MD Moffitt cancer centerTampa, FloridaAlan F. List, MD

Sylvester comprehensive cancer centeruniversity of Miami Miller School of MedicineMiami, FloridaStephen D. Nimer, MDuniversity of Florida Shands HospitalGainesville, FloridaChristopher R. Cogle, MD

GEORGIAemory Winship cancer Instituteemory university School of MedicineAtlanta, GeorgiaAmelia Langston, MDThe blood and Marrow Transplant Program at Northside HospitalAtlanta, GeorgiaAsad Bashey, MD

ILLINOISloyola university chicagocardinal bernardin cancer centerMaywood, IllinoisScott E. Smith, MD, PhDRobert H. lurie comprehensive cancercenter of Northwestern universityFeinberg School of MedicineChicago, IllinoisOlga Frankfurt, MD

� Available cytogenetics and/or molecular genetics

� Ongoing research, including InstitutionalReview Board–approved clinical trials

� Documentation of peer-reviewedpublications in the field

Please contact the Foundation for further information and an application form for your center.

The following centers have qualified as MDS Centers of Excellence:

MDS CENTERS OF EXCELLENCE

Would you like your treatment center to become part of the referral systemfor MDS patients and be designated as a Center of Excellence?

Our MDS Centers of Excellence are institutions that meet the highest standards for diagnosis,treatment and patient care. Your Center helps form the referral base for patients seeking first orsecond opinions and/or additional treatment options from experts in MDS. We currently have 67Centers in the United States and 107 Centers in countries around the world. Our MDS Centers canbe viewed here: https://www.mds-foundation.org/mds-centers-of-excellence

benefits of membership include recognition as an MDS Center of Excellence by the MDS Foundation. Our MDS Centers of Excellenceare recorded in our published newsletters and on the Foundation’s website. For many centers, the acknowledgement attracts patients who are seeking high-quality, MDS specific care, allowing these patients accessto the latest programs and leading-edge thinking and treatment of the disease. Patient referrals through our Patient Liaison to the Centerare a direct result of this recognition. The membership dues support the Foundation’s mission and provide physicians with discountedregistration rates for our biennial International MDS Symposium, as well as a reduced rate for subscription to Leukemia Research.

UNITED STATESARIZONAMayo clinic HospitalScottsdale, ArizonaRaoul Tibes, MD, PhDLisa Sproat, MDThe university of Arizona cancer centerTucson, ArizonaRavi Krishnadasan, MD, FACP

CALIFORNIAcedars-Sinai Medical centeruclA School of MedicineLos Angeles, CaliforniaH. Phillip Koeffler, MDcity of Hope National Medical centerDuarte, CaliforniaStephen J. Forman, MDMoores cancer center at theuniversity of california, San DiegoRafael Bejar, MD, PhDPeter Curtin, MDStanford university Medical centerStanford, CaliforniaPeter L. Greenberg, MDuclA center for Health SciencesLos Angeles, CaliforniaGary J. Schiller, MD

34

Rush university Medical centerChicago, IllinoisJamile Shammo, MDuniversity of chicago Medical centerChicago, IllinoisRichard A. Larson, MD

INDIANAIndiana universitySimon cancer centerIndianapolis, IndianaLarry Cripe, MD/Hamid Sayar, MD, MS

IOWAThe university of Iowa Hospitals and clinics, Holden cancer centerIowa City, IowaCarlos E. Vigil-Gonzales, MD

MARYLANDJohns Hopkins university School of MedicineBaltimore, MarylandAmy Elizabeth DeZern, MDuniversity of Marylandgreenebaum cancer centerBaltimore, MarylandMaria R. Baer, MD

MASSACHUSETTSDana-Farber cancer InstituteBoston, MassachusettsRichard M. Stone, MDDavid P. Steensma, MDBenjamin Ebert, MD, PhDMassachusetts general Hospital cancer centerBoston, MassachusettsTimothy Graubert, MDTufts university School of MedicineTufts Medical centerBoston, MassachusettsKellie Sprague, MD

MICHIGANbarbara Ann Karmanos cancer InstituteWayne State universityDetroit, Michigan Charles A. Schiffer, MDWilliam beaumont Hospitalcancer centerRoyal Oak, MichiganIshmael Jaiyesimi, DO

MINNESOTAMayo clinicRochester, MinnesotaMark R. Litzow, MD

university of Minnesota Medical center, Fairview universityof Minnesota Medical SchoolMinneapolis, Minnesota Erica D. Warlick, MD

MISSOURIWashington university School of MedicineSiteman cancer centerSt. Louis, MissouriJohn F. DiPersio, MD, PhD

NEBRASKAuniversity of Nebraska Medical centerOmaha, NebraskaLori Maness, MD

NEW HAMPSHIREDartmouth-Hitchcock Medical centerand Norris cotton cancer centerLebanon, New HampshireKenneth R. Meehan, MD

NEW JERSEYThe cancer center of Hackensack university Medical centerHackensack, New JerseyStuart Goldberg, MD

NEW MEXICOuniversity of New Mexico comprehensive cancer centerAlbuquerque, New MexicoCecilia Arana Yi, MD

NEW YORKAlbert einstein cancer center/Albert einstein college of Medicine of yeshiva universityBronx, New YorkAmit Verma, MDcolumbia university Medical centerNew York, New YorkAzra Raza, MDMemorial Sloan-Kettering cancer centerNew York, New YorkVirginia M. Klimek, MDMonter cancer center/NSlIJ cancer InstituteLake Success, New YorkSteven L. Allen, MDIcahn School of Medicine at Mount SinaiNew York, New YorkLewis R. Silverman, MDNew york Medical college/Westchester Medical centerZalmen A. Arlin cancer centerValhalla, New YorkKaren Seiter, MD

Roswell Park cancer centerBuffalo, New YorkElizabeth Griffiths, MDJames E. Thompson, MDuniversity of Rochester Medical centerRochester, New YorkJane L. Liesveld, MDWeill Medical college of cornell universityNew york Presbyterian HospitalNew York, New YorkGail J. Roboz, MD

NORTH CAROLINADuke university Medical centerDurham, North CarolinaCarlos M. deCastro, MDWake Forest university School of Medicinecomprehensive cancer centerWinston-Salem, North CarolinaBayard L. Powell, MD

OHIOcleveland clinic Foundation Taussig cancer centerCleveland, OhioJaroslaw Maciejewski, MD, PhDMikkael Sekeres, MD, MSThe Ohio State comprehensive cancercenter, James cancer Hospital andSolove Research InstituteColumbus, OhioAlison R. Walker, MD

PENNSYLVANIAAllegheny Health Network cancer InstituteWestern Pennsylvania HospitalPittsburgh, PennsylvaniaSalman Fazal, MDFox chase cancer centerPhiladelphia, PennsylvaniaPatricia Kropf, MDuniversity of Pennsylvania cancer centerPhiladelphia, PennsylvaniaSelina Luger, MDuPMc cancer centerPittsburgh, PennsylvaniaAnastasios Raptis, MDJames M. Rossetti, DO

TENNESSEEVanderbilt university Medical centerNashville, TennesseeSanjay Mohan, MDMichael R. Savona, MD

3535

TEXASTexas Oncology – San AntonioSan Antonio, TexasRoger M. Lyons, MD, FACPTexas Oncology, MidtownAustin, TexasRichard Helmer, III, MDuniversity of TexasMD Anderson cancer centerHouston, TexasGuillermo Garcia-Manero, MDHagop Kantarjian, MDuniversity of TexasSouthwestern Medical centerDallas, TexasRobert H. Collins, Jr., MD, FACP

UTAHuniversity of utahHuntsman cancer InstituteSalt Lake City, UtahPaul J. Shami, MD

WASHINGTONFred Hutchinson cancer Research center university of WashingtonSeattle cancer care AllianceSeattle, WashingtonJoachim Deeg, MDElihu Estey, MD

WASHINGTON, DCgeorgetown university Hospitallombardi comprehensive cancer centerWashington, D.C.Catherine Broome, MDgeorge Washington universityVA Medical centerWashington, D.C.Charles S. Hesdorffer, MD

WISCONSINAmerican Family children’s Hospitaluniversity of Wisconsin HealthMadison, WisconsinInga Hofmann, MDMedical college of Wisconsinbone Marrow Transplant ProgramMilwaukee, WisconsinParameswaran Hari, MDuniversity of WisconsinMadison Medical SchoolMadison, WisconsinMark B. Juckett, MD

Hospital das clínicas da Faculdade de Medicina da universidade de São PauloSão Paulo, Brazil Elvira D. Rodrigues Pereira Velloso, MD, PhDuniversidade Federal de cearáCeará, BrazilSilvia Maria M. Magalhães, MD, PhDuniversidade Federal de São PauloSão Paulo, BrazilMaria de Lourdes Chauffaille, MD, PhD

CANADAPrincess Margaret HospitalToronto, Ontario, CanadaKaren Yee, MDToronto SunnybrookRegional cancer centreToronto, Ontario, CanadaRichard A. Wells, MDuniversity of TorontoHospital for Sick childrenToronto, Ontario, CanadaYigal Dror, MD

CHINAguangdong general Hospital &guangdong Academy of Medical Sciences Guangzhou, ChinaXin Du, MD, PhDInstitute of Hematology and blood Diseases Hospitalchinese Academy of Medical SciencesTianjin, ChinaZhijian Xiao, MDThe First Affiliated Hospital of Soochow university Jiangsu Institute of HematologyJiangsu Province, ChinaSuning Chen, MD, PhDThe First Affiliated Hospital of Zhejiang universityZhejiang Province, ChinaHongyan Tong, MD, PhDThe Sixth Hospital Affliated toShanghai Jiaotong universityShanghai, ChinaXiao Li, MD, PhD

CROATIAclinical Hospital MerkurZagreb, CroatiaInga Mandac Ragulj, MD

CZECH REPUBLICInstitute of Hematology & blood TransfusionPrague, Czech RepublicJaroslav Cermák, MD, PhD

OUTSIDE THE UNITED STATES

ARGENTINASanatorio Sagrado del corazónBuenos Aires, ArgentinaMarcelo Iastrebner, MD

ARMENIAMuratsan university Hospitalcomplex of yerevan State Medical universityYerevan, ArmeniaGevorg Tamamyan, MD

AUSTRALIAMonash HealthMonash universityClayton, Victoria, AustraliaJake Shortt, BMedSc, MBChB FRACPFRCPA PhDPeter Maccallum cancer Instituteuniversity of MelbourneEast Melbourne, AustraliaJohn F. Seymour, MDThe Royal Melbourne HospitalParkville Victoria, AustraliaDavid Ritchie, MDuniversity of TasmaniaRoyal Hobart HospitalHobart, Tasmania, Australia

AUSTRIAHanusch HospitalMedical university of ViennaVienna, AustriaMichael Pfeilstöcker, MDMedical university of ViennaVienna, AustriaPeter Valent, MDuniversity Hospital of InnsbruckInnsbruck, AustriaReinhard Stauder, MD

BELGIUMAZ Sint-Jan AVBrugge, BelgiumDominik Selleslag, MDuniversity Hospital leuvenLeuven, BelgiumMarielle Beckers, MD, PhDMichel Delforge, MD, PhD

BRAZILAc camargo Hospital –cancer centerSão Paulo, BrazilLuiz Fernando Lopes, MD, PhD

36

DENMARKOdense university HospitalThe university of Southern DenmarkOdense, DenmarkGitte Birk Kerndrup, MDRigshospitalet National university HospitalCopenhagen, DenmarkKirsten Grønbaek, MDLars Kjeldsen, MD, PhD

FRANCEcentre Henri becquerelRouen university School of MedicineRouen, FranceAspasia Stamatoullas, MDcentre Hospitalier universitaire (cHu) de Angers Service des Maladies du SangAngers, FranceNorbert Ifrah, MDcentre Hospitalier universitaire(cHu) de grenobleGrenoble, FranceJean-Yves Cahn, MDcentre Hospitalier universitaire (cHu) de limoges Hôpital DupuytrenLimoges, FranceDominique Bordessoule, MDcentre Hospitalier universitaire (cHu) de NancyNancy, FranceAgnés Guerci-Bresler, MD, PhDcentre Hospitalier universitaire (cHu) de Tours – bretonneauTours, FranceEmmanuel Gyan, MD, PhDHôpital Avicenne/university Paris XIIIBobigny, FranceCharikleia Kelaidi, MDHôpital cochin/university Paris VParis, FranceFrancois Dreyfus, MDHôpital Saint louis/university Paris VIIParis, FrancePierre Fenaux, MD, PhDChristine Chomienne, MD, PhDHôpital Saint-Vincent de Paul (lille)Lille, FranceChristian Rose, MDInstitut Paoli-calmettesMarseille, FranceNorbert Vey, MDService des Maladies du SangHôpital claude HuriezLille, FranceBruno Quesnel, MD

GERMANYgeorg-August-universität göttingenGöttingen, GermanyDetlef Haase, MD, PhDHannover Medical SchoolMedizinische Hochschule HannoverHannover, GermanyArnold Ganser, MDHeinrich-Heine universität Düsseldorfuniversity HospitalDüsseldorf, GermanyUlrich Germing, MDJohann Wolfgang goethe universitätFrankfurt Main, GermanyGesine Bug, MDKlinikum Rechts der IsarTechnical university of MunichMunich, GermanyKatharina Götze, MDMll Münchner leukämielabor Munich, GermanyTorsten Haferlach, MDRems-Murr-Klinik WinnendenWinnenden, GermanyStefani Parmentier, MDSt. Johannes HospitalHeinrich-Heine universität Duisburg, GermanyCarlo Aul, MD, PhDAristotle Giagounidis, MD, PhDuniversity of Heidelberg Medical center St. lukas Klinik SolingenSolingen, GermanyUlrich Mahlknecht, MD, PhDAlbert-ludwigs-universität FreiburgFreiburg, GermanyMichael Lübbert, MD, PhDuniversität HamburgHamburg, GermanyNicolaus Kröger, MD, PhDuniversitätsklinikum carl gustav carusDresden, GermanyUwe Platzbecker, MDuniversity children’s HospitalFreiburg, GermanyCharlotte Niemeyer, MDuniversity of cologneCologne, GermanyKarl-Anton Kreuzer, MDuniversity Hospital MannheimMannheim, GermanyWolf-Karsten Hofmann, MD

GREECEPatras university HospitalPatras, GreeceArgiris Symeonidis, MDuniversity of Athens laikon HospitalAthens, GreeceNora Viniou, MDuniversity general Hospital AttikonAthens, GreeceVassiliki Pappa, MD

HUNGARYSemmelweis university School of MedicineBudapest, HungaryJudit Várkonyi, MD, PhD

INDIATata Medical centre Kolkata, IndiaCol (Dr.) Deepak Kumar Mishra, MDTata Memorial HospitalMumbai, IndiaPurvish Parikh, MD

IRELANDAdelaide and Meath HospitalDublin, IrelandHelen Enright, MD

ISRAELTel-Aviv Sourasky Medical centerTel-Aviv, IsraelMoshe Mittelman, MDchaim Sheba Medical centerTel Hashomer, IsraelDrorit Grizim Merkel, MD

ITALYcancer center – IRccS HumanitasResearch HospitalMilan, ItalyMatteo G. Della Porta, MD centro di RiferimentoOncologico di basilicata (cROb)Rionero in Vulture (PZ), ItalyPellegrino Musto, MD Istituto di ematologiauniversita’ cattolica Sacro cuoreRome, ItalyGiuseppe Leone, MDPoliclinico Tor VergataRome, ItalySergio Amadori, MD/Maria Teresa Voso, MDS. eugenio HospitalTor Vergata universityRome, ItalyPaolo de Fabritiis, MD/Pasquale Niscola, MD

university of FlorenceAzienda OSP careggiFlorence, ItalyValeria Santini, MDuniversity of Pavia School of MedicineFondazione IRccS Policlinico San MatteoPavia, ItalyMario Cazzola, MD

JAPANKyoto university HospitalKyoto, JapanAkifumi Takaori, MDMetropolitan Research and Treatmentcenter for blood Disorders (MRTc Japan)Tokyo, JapanKiyoyuki Ogata, MD, FACPNagasaki university Hospital School ofMedicine, Atomic bomb Disease InstituteNagasaki City, JapanYasushi Miyazaki, MDSaitama International Medical centerSaitama Medical universityHidaka, Saitama, JapanAkira Matsuda, MDTokyo Medical collegeTokyo, JapanKazuma Ohyashiki, MD, PhD

KOREAcatholic blood and MarrowTransplantation centerThe catholic university of KoreaSeoul, KoreaYoo-Jin Kim, MDSeoul National university HospitalSeoul National university college of MedicineSeoul, KoreaDong Soon Lee, MD, PhDyonsei cancer centre, Severance Hospitalyonsei university college of MedicineSeoul, KoreaJune-Won Cheong, MD, PhD

THE NETHERLANDSRadboud university Nijmegen Medical centerNijmegen, The NetherlandsSaskia M.C. Langemeijer, MDVrije universiteit Medical centerAmsterdam, The NetherlandsArjan A. van de Loosdrecht, MD, PhD

POLANDJagiellonian university collegium MedicumKraków, PolandAleksander Skotnicki, MD, PhD

PORTUGALHospital de Santa MariaLisbon, PortugalJoao F. Lacerda, MD

SAUDI ARABIAKing Faisal Specialist Hospital & Research centreRiyadh, Saudi ArabiaAmr Hanbali, MDKing Khaled university HospitalKing Saud universityRiyadh, Saudi ArabiaAk Almomen, MD

SINGAPORESingapore general HospitalAloysius Ho, MD

SOUTH AFRICAuniversity of cape Towngroote Schuur HospitalCape Town, South AfricaNicolas Novitzky, MD, PhD

SPAINHospital universitario de SalamancaSalamanca, SpainConsuelo del Cañizo, MD, PhDHospital universitario la FeValencia, SpainMiguel A. Sanz, MD, PhDHospital universitario Vall d’Hebronlaboratorio del citologia-citogéneticaBarcelona, SpainMaria Teresa Vallespi-Sole, MD, PhD

SWEDENKarolinska Institute atKarolinska university Hospital HuddingeStockholm, SwedenEva Hellström-Lindberg, MD, PhD

SWITZERLANDbasel university HospitalBasel, SwitzerlandJakob R. Passweg, MD, MSbern university Hospital and university of bernBern, SwitzerlandNicolas Bonadies, MDuniversity Hospital ZurichZurich, SwitzerlandMarkus G. Manz, MD/Stefan Balabanov, MD

TAIWANchang gung Memorial Hospitalchang gung universityTaoyuan, TaiwanLee-Yung Shih, MD

National Taiwan university HospitalTaipei, TaiwanHwei-Fang Tien, MD, PhD

THAILANDKing chulalongkorn Memorial HospitalPathumwan, Bangkok, ThailandTanin Intragumtornchai, MD

TUNISIAHospital Aziza OthmanaTunis, TunisiaBalkis Meddeb, MD

TURKEYAnkara university School of Medicine HospitalAnkara, TurkeyOsman Ilhan, MD

UKRAINEResearch center for Radiation MedicineKiev, UkraineDimitry Bazyka, MD

UNITED KINGDOMAberdeen Royal InfirmaryAberdeen university School of MedicineForesterhill, Aberdeen, ScotlandDominic Culligan, MDchristie NHS Foundation TrustManchester, United KingdomMike Dennis, MDDan Wiseman, MDKing’s college london &King’s college HospitalLondon, United KingdomGhulam J. Mufti, DM, FRCP, FRCPathQueen elizabeth Hospitaluniversity Hospital birmingham NHS TrustBirmingham, United KingdomManoj Raghavan, MDRadcliffe Hospitals and university of OxfordOxford, United KingdomParesh Vyas, MD Royal bournemouth HospitalBournemouth, United KingdomSally Killick, MDSt. James’s university HospitalSt. James’s Institute of OncologyLeeds, United KingdomDavid T. Bowen, MDuniversity Hospital of WalesCardiff, WalesJonathan Kell, MD

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38

OUR CAREGIVER STORIES

COPING AND CARING

We hope you will join us at our nextgathering on Saturday, April 29,2017, 1–4 pm at the White DogCafé in Philadelphia.

Kindly register by April 21st bycalling 1-800-637-0839 or emailahassan@mds-foundation.org.

The MDS Family:Coping and Caring EventsRochelle Ostroff-WeinbergWynnewood, Pennsylvania

Coping and Caring LuncheonNovember 5, 2016

MDS patients and their familiesgathered at the Craftbar Restaurant in NewYork City for a wonderful luncheon onNovember 5th, 2016. Guest speaker wasSarah Kelly, MSW, LCSW (OncologySocial Worker). Ms. Kelly’s specialty is oncancer quality of life and psychosocialwellbeing issues.

39

The Importance of Research and Clinical TrialsPage l. WingfieldDurham, North Carolina

I’m sure that if you are reading thispublication, you are aware of theimportance of research and clinical trials.By sharing our story, my hope is you cansee their value from a real life perspective.

In 1970 my husband Neal and I hadbeen married for six short months when hewas diagnosed with Stage IIIB HodgkinsDisease. At that time the expected survivalrate was only two years, and radiation wasthe sole treatment available. However,there were promising clinical trials beingheld at the National Institutes of Health inBethesda, Maryland. Neal was fortunate tobe the last subject enrolled in a studytesting the efficacy of a four drug treatmentreferred to as MOPP. It was a most difficultchemotherapy treatment, but he was one ofthose who reacted favorably to the drugsand his Hodgkin’s Disease was broughtinto remission. As years passed and hisremission held steady, we were able tobuild a life for ourselves.

became a United Methodist pastor, servingfor 18 years. As far as I am aware, Nealmay have been one of the longest post-MOPP therapy survivors, living forty twoyears past his treatment.

In 2009, after more than a year spentseeking medical help for extreme fatigueand shortness of breath, a diagnosis of low-risk MDS was made. His MDS involvedthe red blood cells only, so for a while hereceived occasional transfusions anderythropoietin shots to stimulate red bloodcell production. At first the doctorsconsidered his MDS to be de novo (noknown cause) because of his longremission from Hodgkins Disease.However, they later determined that it wasindeed secondary to his previouschemotherapy.

Because of his age and medical history,he was not considered a good candidate fora bone marrow or stem cell transplant.Instead, he was treated first with Vidazaand then Revlimid. Revlimid worked forover one year, making him transfusionindependent. When Revlimid stoppedworking our last hope was to once againenter a clinical trial. We traveled to DukeUniversity Hospital and met with theprincipal investigator of the study.However, a second miracle was not to be.In January 2012, shortly after our trip toDuke, MDS claimed his life.

I am so grateful for all the years we hadtogether and the research and clinical trialsthat made it possible. All those who worktirelessly in research labs, and those whoconduct and participate in clinical trials aretrue heroes. Their efforts and God’s gracegave us a wonderful life together.

OUR CAREGIVER STORIES

The need for research

and clinical trials is

never ending. Today's

cutting edge treatments

depend in part on your

willingness to take that

leap of faith and

participate in clinical

trials you are eligible for.

We were given the precious gift oftime... to have a family, raise our childrenand enjoy a full life together. He workedfor NIH for twenty-three years, and then hefollowed the true calling of his life and

The need for research and clinical trialsis never ending. Today’s cutting edgetreatments depend in part on yourwillingness to take that leap of faith andparticipate in clinical trials you are eligiblefor. Increasing the body of knowledge willtake us to a cure for MDS....and all cancers!

40

My Journey With MDSRose ZumbielEdgewood, Kentucky

My MDS Journey began in 1997 on abeautiful summer afternoon while sittingon my porch in my northern Kentuckyhome enjoying my day. I noticed that I hadseveral large bruises on my legs andbecame concerned so I decided to see myfamily practice doctor. I wasn’t veryworried since I felt fine.

My doctor ordered a CBC test and theresults came back showing a low plateletcount. I had a cold just prior to the test andmy doctor attributed the cold to my lowplatelets. However, he asked that I repeatthe CBC test in six months. So, in 1998, Ihad another CBC test but this time theplatelet count came back even lower at150,000, the low end of the normal range.My doctor then told me I should see ahematologist oncologist but even afterbeing told that, I didn’t realize how seriousthis condition could be.

In 1999 I went through my first bonemarrow procedure. I was quite nervous,even scared, and it turned out to be asunpleasant as I feared. But the results wereeven more unnerving….being told I had arare blood disease. I was told they didn’thave a name for it and the disease mostlyimpacted the elderly. I was just 48 at thetime and I worried about the impact on myhusband, Bill, our three adult children and,

was in the progression of the disease. Myplatelets came back at 87,000 which wasvery scary. But Dr. Bhandari also had a“wait and see” approach but I nowunderstood this is how you initially dealwith this disease. So, I tried to get asmentally comfortable as I could in dealingwith my MDS. I learned to make and selljewelry and stay busy with our boat storagebusiness. And, with three married childrenand now five grandchildren, all living withinten miles of us, it was getting easier in notthinking about my disease all the time.Nevertheless, I prayed daily that this diseasewith its bruising and fatigue side effectswould go away. But, overall, life was good.

In 2005 Bill retired and I lost mymedical insurance due to my pre-existingcondition (MDS) and was not able to getnew insurance right away. This was a majorworry which proved warranted. During anormal check-up with Dr. Bhandari, henoticed new spots on my legs. I didn’tthink much of them but he did and orderedan immediate bone marrow procedure.Results showed my platelets dropped downto 30,000. Now this was bad! He firstordered platelets for me to see if that wouldhelp. But after just one week, all of thesenew platelets were gone and I was back to30,000. Now, fortunately, with newinsurance from our State’s high risk Plan,the next step was my going to our localhospital’s cancer care center. There, I hadan infusion of a drug, whose name I can’trecall. Anyway, I was allergic to the drugso the procedure was halted.

FAMILY STORIESOUR PATIENT STORIES

PATIENT STORIES

at that time, three grandchildren. I justcouldn’t imagine what would happen next.

Sometime over the next few years, Ilearned the name of my disease wasmyelodysplastic syndrome or MDS forshort. Looking into it more deeply, I foundout it was caused by benzene poisoning.But I didn’t understand. I had never, to myknowledge, been exposed to benzene in mylife. Yes, my parents were both heavysmokers and it crossed my mind thatperhaps that brought it on. But my siblingsdidn’t have MDS and neither did myparents. This didn’t make sense.

Several more years passed and I wasbruising like crazy! Other than being tiredand feeling run-down throughout the day,bruising was my only noticeable symptom,again, being caused by my low platelets.My doctor just seemed to have a “wait andsee” attitude and approach to my condition.I did not! I couldn’t understand that if myplatelets were dropping, why couldn’tsomething be done to bring them back up.

So, I decided in 2004 to find a newdoctor and that’s when Bill and I met Dr.Manish Bhandari. I knew right away thatDr. Bhandari would help me. He was kindand compassionate and I really felt he hadmy interests at heart. He is just a wonderfuldoctor. He performed my second bonemarrow procedure to determine where I

41

It was now 2007 and Dr. Bhandariordered an infusion of a new chemo drug,Vidaza. However, we were getting ready toopen a beauty salon with our daughter so Ididn’t really want to start taking the chemoat that time. Therefore, I held off in takingVidaza and we opened the salon where Icould place my jewelry and help run thebusiness. I loved it!

But the next year I felt I couldn’t holdoff from taking the Vidaza any longer so Ibegan treatment. It involved taking 21shots one week each month for six months.After six months, my platelets hadincreased to 57,000 so Dr. Bhandaristopped the Vidaza treatments to see whatwould happen. Over the next six months,my platelet levels moved around butgenerally increased so that by 2009 theywere up to 86,000. This was great and I feltgood. Over the next 2 years I continued toworry and also prayed a lot that the levelswould continue to increase. They seemedto bounce around so much so that Dr.Bhandari dubbed me “The Bouncer”. Buttheir range stayed around 56,000 – 87,000.

My bruising, however, was gettingworse. Therefore, I decided to call theMDS Foundation to seek out their adviceand determine if my bruising was commonamong others with MDS. I spoke withAudrey Hassan who suggested I go to oneof their Centers of Excellence in the UnitedStates. We learned one was within twohours in Indianapolis at the IU CancerCenter so I made an appointment with Dr.Larry Cripe. I had previously discussedwith Dr. Bhandari my interest in thissecond opinion and Dr. Bhandari said thatif he had the condition I have, he’d want toget a second opinion also. Dr. Bhandarisent all my bone marrow reports andinformation to Dr. Cripe. Bill and I saw Dr.Cripe in August 2011. Dr. Cripe was verythorough and professional, reviewed all thematerial sent to him and gave me anexamination. While waiting to hear Dr.Cripe’s analysis I prayed that he wouldhave an answer about my bruising and

when he came back to see me he did! Hesaid he could understand why Dr. Bhandaricalled my condition MDS when looking atmy bone marrow but he believed I had anauto immune disease mimicking MDS!Well, when he said that, I felt I had a hugeweight lifted off my shoulders. This wasgreat! I just couldn’t believe it and askedhim to send his findings to Dr. Bhandari.

On the drive back home Bill and Italked and were stunned that I didn’t haveMDS. When I saw Dr. Bhandari a coupleweeks later I asked him what he thought.He said he and Dr. Cripe were bothcorrect…I have both MDS and an autoimmune disease. I was confused andlooked at him and said “Really?” He saidYes and I said “While I love you for all youhave done for me, I am going to believe Dr.Cripe!” Dr. Bhandari laughed and said“Believe whatever helps you best.” Thefact that my condition could be an autoimmune disease is not good. An autoimmune disease can be very serious but notas bad, at least in my mind, as MDS.

However, a short time later myexcitement faded. Dr. Bhandari told methat, after speaking with and reviewing mybone marrow biopsies with Dr. Cripe, theywere in agreement that my 8thchromosome showed I definitely had MDS.Although this news was now definitive andI was quite troubled by it, I accepted it.What choice did I have?

At that time in 2011, my platelet countwas 75,000. Over the next several years,my platelet count continued to bounce upand down but it began trending higher. One

FAMILY STORIESOUR PATIENT STORIES

month it might be 90,000, the next month,80,000, the next month 110,000. But in2016 the range increased even more to110,000 – 150,000. During these years, Icontinued to go about my life, living it tothe best of my ability. By 2016 mygrandchildren count is up to nine and myfamily and jewelry business are keepingme busy and sane.

I’ve continued to pray for my bruising,fatigue and disease to leave me. But inNovember last year, just by happenstance,I became familiar with and started prayingto a modern-day saint, St. Padre Pio, whohas performed many miracles. I would prayto him off and on throughout the weekwhenever I would think of him. About amonth after I started praying to him Ireceived unsolicited in the mail a prayercard and chaplet from The St. Padre PioFoundation. I was shocked! It was like St.Padre Pio himself was asking me to use theprayer card and chaplet to pray to him. So,I began praying to him every night forhealing from this disease. In late DecemberI saw Dr. Bhandari for my normal checkupwhere he again did a CBC and plateletcheck. When I learned that my plateletcount was an all-time high of 182,000, Isought out Dr. Bhandari. I was so excited!When I saw him he sat me down and said,“Rose, I believe there has been a miracle!”I was stunned. I couldn’t believe it. He said“I don’t know how but you are cured.” I satthere in shock. I was cured. It was amiracle! He shook my hand and said he’dsee me in six months just to touch base.Now, I do believe in miracles. I prayedhard and often over the years and believePadre Pio had a hand in my healing alongwith Dr. Bhandari.

Today I feel great. I am still tired andthe bruising continues. Dr. Bhandari said itwould because the bone marrow isdamaged. But I look at the bruising andfatigue as my cross to bear. I still prayevery day. I hope everyone reading thisfeels hope on their journey and I will bepraying for all of you.

42

From Nothing AboutMDS in Danish –To Being Part of theGrowing Danish Patient Society LyleNiels JensenSlangerup, Denmark

More than ten years ago when I wasdiagnosed with MDS—MyelodysplasticSyndromes—there was no information inDanish about MDS on the Internet.However, luckily, I managed to findseveral websites about MDS in English.Having lived and worked in Canada andwith my wife, Anna, being Canadian weread those websites with great interest theday after having celebrated our 23rd yearwedding anniversary. The Englishlanguage websites were plenty for me, butAnna yearned to talk with others during thebeginning stages of great uncertainty in myMDS diagnosis.

Here is the story of the journey from(almost) nothing about MDS in Danish toMDS now being an active and visible partof the growing Danish patient associationLyle.

Already in the summer of 2008, theMDS Foundation hosted a morningmeeting for MDS patients and relatives atthe Copenhagen Marriott Hotel with theopportunity to meet other MDS patientsand their families. My doctor atRigshospitalet made me aware of themeeting, and it was my first contact withthe MDS Foundation. The Keynote speakerwas Dr. Lars Kjeldsen of the Hematology

Clinic at Rigshospitalet, and I alsoremember the president of Lyle, JytteGamby, being there to invite those presentto join the then less than a year oldassociation for lymphoma and leukemiapatients. I did not entertain the idea ofjoining at that time. I did not have such adangerous disease, so I thought: I don’tbelong there!

Building an International Networkvia the MDS Foundation

Two years later, I contacted the MDSFoundation and with my input we workedtogether to update the MDS Foundation’swebsite. Many email exchanges later anddiscussions via Skype across the Atlanticwith Bob Weinberg, a member of the MDSFoundation’s Board of Directors, resultedin a more user-friendly modern version oftheir previous website. During this time, Ialso acquired the domain mds and you.info.

Another result of the contact with theMDS Foundation in 2010 was that thefollowing year I was invited to twomeetings. The first was a family day forMDS patients and relatives during their11th International Symposium onMyelodysplastic Syndromes in Edinburgh.The day ended with a 2-hour meetingregarding the need to establish MDS-specific patient groups worldwide. Duringthat meeting, I learned about patients’associations in England and in France. Thesecond meeting was a two-day Celgeneevent in Munich under the heading“Partners for Progress” (see participants inthe photo above), which was about the rare

cancers. During that event, I learned aboutdifficulty getting newer drugs to EasternEuropean countries and the initiative MDSLife Beyond Limits, which was largelyfunded by Celgene. On the return fromthese meetings, I started the website DKMDS Patient Support Group in the fall of2011. The logo of my group was inspiredby the MDS Foundation’s logo. And withCelgene Denmark’s help, we createdpostcards for potential new members tocontact the group. These postcards werethen distributed to the hematologicalcenters around the country.

Later in 2012, I attended a Lyle hostedevent in Copenhagen and announced theidea of creating a Danish association forMDS patients and relatives. I stillremember one patient’s gripping taleduring the meeting about her bone marrowtransplant at Rigshospitalet, and her remarkafter having attended the first minutes ofmy little after meeting: “Good luck withthe project. I am cured, so I’m notinterested in an association of MDSpatients”. There were maybe about 25– 30participants at the small after meeting andmy contacts in Celgene Denmark had toldme that around 200 to 300 patients a yearwere confronted with the diagnosis ofMDS in Denmark. Based on this and thesurvival curves, which I had seen invarious medical articles, I then estimatedthat there were around 800– 1000 peopleliving with MDS in Denmark. I wassomewhat optimistic and thought at thattime that the new association could easilyget 200 to 300 members to join.

FAMILY STORIESOUR PATIENT STORIES: AN UPDATE

43

The First Meetings for MDSPatients and Relatives WereSuccesses

In the Spring of 2013, the first meetingfor MDS patients and relatives was held inconjunction with the Novartis Iron Summitat the Bella Center that year. There werethree speakers: Dr. Lars Kjeldsen fromRigshospitalet in Copenhagen, Dr. NorbertGateman from Heinrich Heine UniversityHospital in Germany and Dr. Richard Wellsfrom Sunnybrook Health Sciences Centrein Canada. About 60 people registered forthe event of which about 45 showed up. Inthe picture above Dr. Richard Wells speaksabout the myths of MDS.

The next meeting, which was held atRoskilde Hospital in January 2014, was aneven bigger success with over 70 peopleregistering for the event and about 60 ofthem finding the way to the hospitalauditorium. Guest speakers were consultantKlas Raaschou Jensen from the local hospitaland Dr. Theo de Witte from the Netherlands,who was in Roskilde to attend a meeting ofDanish hematologists. Dr. Theo de Witte’spresentations were given in English, buttranslated into Danish by interpreter.

The image below shows a loved onesupporting a MDS patient during themeeting in Roskilde.

Claus Werenberg Marcher from UniversityHospital and Professor Detlef Haase fromGeorg August University of Göttingen askeynote speakers was even less. What Imost remember from that meeting was thevery inspirational nurse, Winnie Krejsing,which Dr. Marcher had brought along, aswell as the subsequent conversation withDr. Haase about the importance of researchfor the future treatment of MDS patients. Aplanned meeting in Aalborg had to becanceled due to little interest.

Our finances were rather limited. Wehad received a startup grant from the MDSFoundation and had entered into a fewcollaboration agreements with Novartis.These agreements allowed us to use thecommunications company Geelmuyden.Kiese to perform all the practical work inconnection with our meetings, such ascontacting speakers to arrange dates andtravel, finding a venue, drafting aninvitation and getting printed anddistributed, registering people wanting tocome to the meeting, and arrangingtranslation of foreign speakers to Danish.

Time to Find Partners NationallyBased on these developments, the MDS

DK Patient Support Group Board decidedto explore cooperation opportunities inDenmark. In spring 2015, the board held ameeting with the Danish Cancer Society,who told us that we could well achieve thestatus of a network under them, but theywould recommend a look at otheropportunities for cooperation. This resultedin a meeting between board members from

MDS DK Patient Support Group and boardmembers from Lyle in late summer 2015.The participating board members fromMDS DK Patient Support Group were veryhappy with the meeting, and the boarddecided to seek our activities continuedunder the auspices of the patient societyLyle and thus discontinue MDS DK PatientSupport Group as an independentassociation. Subsequently, I attended aboard meeting in Lyle, which was a verygood experience. The board decision wasendorsed at our annual general meeting inthe autumn, and then the way was open fora binding cooperation.

At the same time internationalcooperation was intensified. MDS DKPatient Support Group became an associatemember of the MDS Alliance andparticipated in a Novartis Iron OverloadPatient Advisory Board meeting in Berlin.

At Lyle’s general meeting on April 1,2016, I was elected to Lyles board. ThenMDS DK Patientsupport group held as ourstatutes prescribe an extraordinary generalmeeting on 13 April at Karens MindeCulture House, where the autumn decisionon the association’s abandonment wasconfirmed. So now, the activities of MDSDK Patient Support Group is part ofsomething bigger, namely the growingpatient association Lyle fully in line withwhat Celgene CEO recommended atPartners for Progress in Barcelona in 2012:Go together across diseases and borders,and stand stronger against politicians andcompanies both nationally andinternationally.

FAMILY STORIESOUR PATIENT STORIES

Then interest seemed to evaporate. At ameeting in Stakladen in Aarhus with Dr.Eva Hellström Lindberg from Karolinska inSweden as keynote speaker and a whisperinterpreter who translated from Swedish toDanish only 25 of the 45 registeredparticipants showed up. Attendance at thenext meeting in Odense with consultant

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What Has MDS DK PatientSupport Accomplished?

In its few years of existence, MDS DKPatient Support has created a website,which provides information about MDS inDanish both for the newly diagnosed andfor those who have been living with MDSfor some time. This will continue under thepatient association Lyle.

Month after month, we have attemptedto bring information about the latestresearch development around MDS mainlybased on the periodical Leukemia Researchand the Google+ group Advances inMedicine and Biology. This will continueunder the patient association Lyle andexpand to other information sources.

We took initiative through Celgene tohaving the website MDS Life BeyondLimits available in Danish and otherScandinavian languages. After publicationof the MDS Foundation’s patient booklet inDanish on our website, Celgene took theinitiative to create the website blodceller.dkspecifically aimed at the newly diagnosedMDS patients and their relatives also in allScandinavian languages. The informationon this website is also available in printedform through the patient society Lyle. Ourlatest finished project is the Danishtranslation of the MDS Foundation’sbooklet “What Does My Bone MarrowDo?”, and it is available for distribution topatients and their caregivers in Denmark,and will in the near future also be availableas a downloadable PDF file on the websitedkpsg.mds and.you.info.

In 2015, in a last minute membershipdrive we also created a postcard toadvertise our website which wasdistributed to Danish hematological centersin a holder. Some people on the picture areMDS patients and some are not. Thispostcard was financed by the startup grantfrom the MDS Foundation.

What I Bring to the PatientSociety Lyle

What am I bringing to Lyle? I have aninterest in delving into the latest scientific

breakthroughs in medical research. Mybackground as a chemical engineer makesthis possible. Until the middle of 2015, myfocus was only on articles that specificallymentioned MDS, but recently interest hasspread to other abbreviations such as AML,ALL, CLL, CMML abbreviations, which Ihope to get a little more knowledge ofduring the coming months. In addition, Iam interested in photography and for whatis happening in Danish politics. Thoseinterested can read more about that on myGoogle+ pages and see some of my photo

FAMILY STORIESOUR PATIENT STORIES

on 500px. Besides the website www.mds -and you.info with links to MDS groupsworldwide and a world map of MDSCenters of Excellence and the websitedkpsk.mds and you.info, I am alsowebmaster of a few other websites so ITtakes up a little in my everyday life. Ineveryday life, I use mainly computers withthe operating system openSUSE, which isbased on the same core code as most of theworld’s supercomputers. Over the pastyears, I find that I am increasingly usingbrowser based tools, which also works onmy smartphone or tablet.

I share the hope of the Chairman of Lylethat this patient support group eventuallywill develop into a support organisation forall blood cancer patients in Denmark.Including adding MDS to diseases such asAML, ALL, CMML is a step in thatdirection. As is the structure, which theboard of Lyle have created to deal withmany diseases.

The idea behind the picture is that one cannot identify who has MDS. Three people inthis picture have been diagnosed with MDS. Patients are sometimes hurt by commentsalong the lines of “but you don’t look sick.”

DANISH MDS AWARENESS POSTCARDS

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WillWeexhaust all possibilities.

Celgene Patient Support® provides free and personalized assistance with patients’ access and reimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support® Specialist will streamline access to Celgene products by helping you and your patients with:

Benefits investigation

Prior authorization

Appeal support

Medicare

Co-pay assistance – Celgene Commercial Co-pay Program – Co-pay assistance through third-party organizations

Prescription status

Celgene free medication program

Celgene products and restricted distribution programs

To Contact Celgene Patient Support®:

Call: 1-800-931-8691

E-mail: patientsupport@celgene.com

Fax: 1-800-822-2496

Visit: www.CelgenePatientSupport.com

Monday through Friday, 8:00 AM to 7:00 PM ET

4 out of 5 patients who requested assistance from Celgene Patient Support ® received their medication.

Celgene Patient Support® is a registered trademark of Celgene Corporation.© 2013 Celgene Corporation 09/13 US-CELG110059(1)

We will…because patients are our priority.

WillWeexhaust all possibilities.

Celgene Patient Support® provides free and personalized assistance with patients’ access and reimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support® Specialist will streamline access to Celgene products by helping you and your patients with:

Benefits investigation

Prior authorization

Appeal support

Medicare

Co-pay assistance – Celgene Commercial Co-pay Program – Co-pay assistance through third-party organizations

Prescription status

Celgene free medication program

Celgene products and restricted distribution programs

To Contact Celgene Patient Support®:

Call: 1-800-931-8691

E-mail: patientsupport@celgene.com

Fax: 1-800-822-2496

Visit: www.CelgenePatientSupport.com

Monday through Friday, 8:00 AM to 7:00 PM ET

4 out of 5 patients who requested assistance from Celgene Patient Support ® received their medication.

Celgene Patient Support® is a registered trademark of Celgene Corporation.© 2013 Celgene Corporation 09/13 US-CELG110059(1)

We will…because patients are our priority.

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CONTRIBUTIONS TO THE MDS FOUNDATION

Robert Allard • Frances R. Applebaum •Rodney Armstrong Jr. • Richard andSusan Baldwin • Kathleen Barnett •Steven Bechtel • Charles M. Bell •Benita Berman • Robert Brickner •Cynthia Brossman • Jan Brown • AnneCahn • Tom and Laura Cammarota •David Carden • Jeanne Carden • DonaldCariani, MD • Livio Ciaralli • JessicaConley • Jane Connelly • Fred Constantine• Janice Cook • Susan E. Cook • LindaDay • Stuart and Vera Deniston • MarkDe Noble • Martha De Noble • MarilynDickstein • Dennis D. Dillon • Rogersand Kathy Dixson • Jean Elli • CharlotteEllner • Diana L. Feit • Shayle Fox •Dorothea Fradkin • William Frost •Vanessa Locher Fry • Andrew O.Feuerstein • Margaret Gavin • AndyGlasgow • Robert Glasgow • Benja Good• Natalie Greenberg • Peter L. Greenberg• Terry Grigg • W.C. Hall, Jr. • WilliamHamilton • Ralph A. Hamaker • PeteHanna • Renee Hanna • Sally Hanna •Cindy Hardee • John U. Harris, Jr. •Mary Haynes • Alice Healy • MargeryAnn Heath • John and Joan Heine • LindaHibbert • Patricia Hille • MelindaHopper • Leonard A. Jewler • Barry

Johnson • Joseph P. Keenan • ChristaKerkorian • Nancy Killion • MichelleKing • Joseph and Claudia Kotowicz •Raymond Kuehl • Kevin Lawlor • CarolA. Lovell • William G. Lovell • Nancy,Brian and Tara Madden • Sandra Madden• Prue Malles • Raymond W. Malles •Lunelle Siegel McCallister • James R.McCloud • Debbie McDermid • HelenaA. Miley • Betty Jane Mincemoyer •Laura Molnar • Larry Moore • PamelaMroczkowski • Jean Naman • Robert R.Nash • Stephen D. Nimer • WendyO’Brien • Frank Y. Parce • Kenton Pate• Janna Pelle • William Pesek • RonPeters • Jerry W. Pike • Diane Plitz •Carol Pomeroy • Carolyn L. Porco •Theodore and Ellen Propp • AnnettePuczkowski • Clement and JoanRancourt • Joe Randazzo • KatherineRadosh • Andrea Reese • EdwinRozendal • Emily Rubinstein • DonaldM. Shachat • Nancy R. Schauer • DanScheuer • Markus Schuetz • GenevieveSharp • William Sharp • Alan and Teri JoShields • Fred Skinner • Claire-ElizabethSloan • Carol Solberg • Ronald Solberg •Thomas B. Snodgrass • Patricia Stohler •Morris and Nancy Storck • Otto Ryan

The MDS Foundation relies on gifts to further its work. We would like to acknowledge the generosity of the following individuals and organizations that have recently provided gifts to the Foundation:

GIFTS TO THE FOUNDATION

THANKYOU...Szanto • Frederick J. Tieuli Jr. • SherriTieuli • Becky Toomay • Judy Traister •Richard Traister • Karen Tschinkel •Marcia Vanderlee • Harold J. VanEssendelft • Ronald and Helen Vanskiver• Yvette Vine • Matthew Warshauer •Virginia Watson • Richard Wayland •Leon Weiss • Kate Welch • Roberta J.White • Warren H. White • Pam Whitmore• Martina Wiedmayer • Cindy Wilcox •J. Thomas Williams, Jr. • Robynne A.Williams • Boyd Winck • Randall Wong• Leonard Yool • Mohammad Zahir,MD • Joanne Zanfardino • P.F.Zanfardino • Rose Zumbiel • Williamand Rosemary Zumbiel

Pioneering science delivers vital medicines™

THANK YOU TO OUR SPONSORS FOR THEIR SUPPORT

ROBERT JAY WEINBERG MEMORIAL

DonationsHave BeenMade By:RochelleOstroff-WeinbergWynnewood, PA

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The MDS Foundation’s Work Helps Keep Memories Alive

Larry Admire • Jennie Agresta • Patricia Agresta • Marjorie Armstrong • Bernard Ashner • Gerard Barbero• Dorothy Bayer • Richard Victor Belluz • Gerald Berman • Judith Bifano • Katrina Blumenstock •Michael S. Boley • Bernice S. Borelli • Richard Botwinick • Joseph Boyd • Donald Brockel • Alvin JudsonBrown, Jr. • Michael Angelo Burdi • William Bynaker • Marie T. Callan • Barbara Callaway • LucyCampbell • H. Gordon Cooper, Jr. • Sarita Coopwood • Charles A. “Bud” Cross • Mary Irene Crowell •Paul Cummins • Edward E. Daley, Sr. • Barbara L. Demers • John Dehnert • Rebecca Lynn Reed Demori• Helen Denton • Thomas DeRolf • Dominic Devito • Mike Dowd • Patricia H. Drotleff • Leman LeoDunlap • Diane Earle • Michael Ehrlich • Arthur H. Epstein • Mark Feeney • Alvin Fisher • Al Foster• Nancy C. Fox • Herbert G. Frey • William Earl “Bill” Fritts, Jr. • Anne M. Gaffney • Kenneth Ganzer •Hector L. Garcia • Milton L. Gerber • James Gilby • Lorraine B. Gleixner • Randy Goodman • DonaldGoers • Rena Gottlieb • Phyllis Gubitosi • Dianne Guinn • Barry Wayne Hall • Margery Ann Heath •Michael Heimes • Martin Heiss • Myra A. Helton • Gloria Hernandez • George M. Herrmann • MarjorieHewett • Chuck Highbaugh • Michael Holmes • Mary Alice Hudzik • Kate Karam • Fred Keiter • CindyKlein • Margaret Klein • Jerry Koen • Jerry Laufer • John “Jack” Lawlor • Albert Lee • Duk Pil Lee •Jacqueline List • David Loeb • Dave Madden • Kathryn Malek • Elefterios Mantas • Fred Matthys • WalterMay • Dolores McFarland • Taylor Moen • Lillian Morris • Daniel J. Mount • Harriett Murphy • WalterMyers • James Riley Nix • John E. Nowlin • Arlene O’Donnell • Norman Osgood • Hong Ou • VirginiaOwen • Madhavbhai B. Patel • George H. Paul • Anthony Pelle • Frank Penrose • Elaine Phillips •Kieran E. Pillion • Charles Pritchard • Theodore S. Ratkus • Bonnie L. Reed • Marlene Reinhart •Antoinette Reiner • Marcia E. Resnik • John J. Rogers • Abraham Rosenthal • Ruth Schmieg • William J.Schneider, Jr. • Dick Schoemer • Karin Schurfeld • Arnold Schwartz • Daniel Sheehan • Marlene Shervey• Nicole M. Shoemaker • Tom “Shu” Shuey • Roy Shumard • Michelle Atwell Smedley • Dale V. Smith •Robert Skelton • Ray Stohner • Patricia Davey Struck • Dave Sundstrom • Bob Swindell • H. FranklinTaylor, III • Joe Thomas • Philip N. Thomas • Robert Todd • Donald Toman • Carol Usher • PaulValenzano • Giuseppe Vieceli • Robert Harrison Wadsworth • William W. Wallis • Lucia G. Warde • NormaWeinberg • Gary Wilson • James Carmen Wright • Ruth E. Zager • Michael J. Zondorak

MEMORIAL FUNDS

Honor or memorialize your loved one at: www.mds.foundation.org/donate orcontact us at 800-MDS-0839 (within uS), 609-298-1035 (Outside uS).

MEMORIAL DONATIONS HAVE BEEN RECEIVED IN THE NAME OF:

LIVING ENDOWMENTS

Living Endowment Donations Have Been Made in Honor of:

Ronald SolbergSubmitted by: Kae Walker, Denny and Donna Gilbertson, Eugene and Janet Hogden, Carina Whitaker, Ronda Solberg, Cynda Solberg

Ruthanne SimonsSubmitted by: Ruthanne & Earl Simons

Jack lawlorSubmitted by: Kevin Lawlor

Antoinette ReinerSubmitted by: Loretta Reiner

Steven bechtelSubmitted by: Dan Bergeron

Don KaneSubmitted by: Jeffrey Kane

bob WolfeSubmitted by: Betsy Burgess

Vicinage XV Management Teamand Mark Sprock

Submitted by: Georgia CurioSheila Martin

Submitted by: Thomas MartinJohn (Jack) lawlor

Submitted by: Kevin Lawlorlynn Oswald

Submitted by: Karen Ruud

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49

Learn more about the MEDALIST Trial at www.clinicaltrials.gov by searching for NCT02631070.

Or request information by e-mail at clinicaltrialdisclosure@celgene.com or call 1-888-260-1599.

©2016 Celgene Corporation All rights reserved. 9/16 Version 1 Celgene Medalist Patient Ad_V1.0_23-Sept-16

in partnership with Acceleron Pharma

IF YOU HAVE MDSof very low–, low-, or intermediate risk and

require regular blood transfusions, you may be eligible to take part in an international clinical

trial called the MEDALIST Trial.

Ask your doctor about the MEDALIST Trial. Together you can decide if this clinical trial

is right for you.

A clinical trial is NOW ENROLLINGMEDALIST is an international clinical trial for people who have myelodysplastic syndrome (MDS). MEDALIST will determine whether an investigational drug called luspatercept* can help

• reduce the number of red blood cell transfusions

• improve the symptoms of anemia associated with MDS

*The safety and efficacy of luspatercept has not been established. There is no guarantee that luspatercept will become commercially available.

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NEW CLINICAL STUDY IN MDS PEVONEDISTAT-2001

Azacitidine Versus Single-Agent Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), and Low-Blast Acute Myelogenous Leukemia (AML).

Takeda Pharmaceuticals International Co. is currently enrolling patients for a Phase 2 clinical trial of the

chronic myelomonocytic leukemia and low-blast acute myelogeneous leukemia.

The study will enroll approximately 117 participants. Once enrolled, participants will be randomly assigned

• Pevonedistat 20 mg/m2 and azacitidine 75 mg/m2 combination• Single-agent azacitidine 75 mg/m2

• 18 years of age or older• Patients have intermediate, high, or very high-risk MDS based on the Revised International Prognostic Scoring System (IPSS-R), a standard prognostic tool, or have CMML•

In order to refer a patient with MDS, CMML, or low-blast AML for enrollment to this study and review eligibility criteria, physicians/health care providers should visit www.clinicaltrials.gov (NCT02610777)

Contact: 1-877-674-3784; globaloncologymedinfo@takeda.com

Pevonedistat is an investigational agent and is not approved by the FDA or other regulatory agencies worldwide as a treatment for any indication.

Takeda Oncology is a trademark of Takeda Pharmaceutical Company Limited. Millennium Pharmaceuticals, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. ©2016 Millennium Pharmaceuticals, Inc.

51

NEW CLINICAL STUDY: IMerge Lower-Risk MDSCurrent Status: Part 1 recruitment complete; Part 2 is not yet open for recruitment. For

additional details, refer to the Geron press release (12Sep2016) at

http://ir.geron.com/phoenix.zhtml?c=67323&p=irol-newsArticle&ID=2201055.

Janssen Research & Development, LLC is conducting a Phase 2/3 clinical study referred to as

“IMerge”, with the study drug Imetelstat, which is a first-in-class telomerase inhibitor. With its

novel mechanism of action, Imetelstat may provide clinical benefit to MDS patients. In this study,

Imetelstat is administered as a 2-hour intravenous infusion every 28 days.

IMerge is a study for people with MDS who need blood transfusions due to anemia (low red

blood cell counts). People with low or intermediate-1 risk MDS that has relapsed or is refractory

to Erythropoiesis-Stimulating Agents (ESAs) treatment are enrolled in the study. This study is

being conducted at multiple hospitals and institutions around the world, in approximately 80

sites globally.

For more information about this clinical study, please visit

www.clinicaltrials.gov (NCT02598661)

63935937MDS3001

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