2
challenge. Despite advances in allo-HSCT reducing risk of morbidity and mortality, relapse has not altered signicantly. We performed a single institution review of relapse following allo-HSCT in patients with AL examining salvage therapy and characteristics of long term survivors. Methods: All adult patients who proceeded to an allo-HSCT for AL from 1998-2012 (n¼100) were reviewed. 24 relapsed following allo-HSCT and a detailed review of salvage treat- ments and outcomes was made. Probability of overall sur- vival (POS) and 95% condence interval (CI) were calculated by actuarial method. Results: The 5 year POS of the 100 patients with AL pro- ceeding to allo-HSCT was 71 % (CI 61-80%). Of 24 relapsing after allo-HSCT, 17 had initial diagnosis AML, and 7 ALL. The AML group median age was 49y (range 22-65), 53% male. Ten patients received sibling donors, 6 unrelated donors and 1 patient a related haplo-identical donor. Relapses were mostly systemic (14) and extra medullary (EM) 3 of the 17 cases. Median time to relapse was 13 months (3-57). Salvage treatments were: second allo-HSCT +/- chemotherapy (chemo) (n¼5); donor lymphocyte infusion (DLI) +/- chemo (n¼5); chemo +/- withdrawal of immunosuppression (WI) (n¼4); or palliative/supportive care (n¼3). Ten patients (57%) achieved complete response (CR), and CR was maintained by 8 patients (47%), with a median follow up 34 months (range 8-66). All deaths (n¼9) were due to disease. All 3 patients with EM relapse are in ongoing remission. In the ALL group (n¼7) median age was 22y (range 19- 52), 57% of male. 3 were sibling donor transplants, 3 unre- lated and 1 patient received a double cord. Relapse was systemic in 5 patients, and EM in 2. Median time to relapse was 13 months (range 3-57). Salvage treatments comprised: chemo +/- WI (n¼3), second allo-HSCT +/- salvage chemo (n¼2), DLI +/- salvage chemo (n¼1), with 1 patient receiving novel monoclonal antibody therapy. Three patients achieved a CR, however, all died, 2 of disease progression. Two patients remain alive in PR with ongoing salvage treatment to be determined. Conclusions: Despite advances in allo-HSCT, long term sur- vival outcomes for patients with ALL who relapse after allo- HSCT remain poor. However, in contrast, for patients with AML who relapse, durable long-term remissions can be achieved with salvage therapy (with and without second allo-HSCT) with almost half of our patients (47%) in ongoing CR at a median of 34 months (range 8-66). As shown in other studies EM relapse, may be salvaged with good long term results. 331 Impact of Invasive Fungal Infections on Mortality, Length of Hospital Stay, and Costs in Allogeneic Hematopoietic Stem Cell Transplant Patients Jenny Cai 1 , Angela Prehn 2 , Haran Schlamm 3 , Massimiliano Mucci 4 , Aimee Ferraro 2 . 1 Anti-infective/Vaccine TA, Safety Evaluation and Reporting, Worldwide R&D, Pzer Inc., Bridgewater, NJ; 2 2. Public Health Program, School of Health Sciences, Walden University, Minneapolis, MN; 3 HTS Pharma Consulting, LLC, New York, NY; 4 Anti-infective/Vaccine TA, Safety Evaluation and Reporting, Worldwide R&D, Pzer Inc., Milan, Italy Background: Over the last decade, unrelated donors have become a vital resource for hematopoietic stem cell trans- plantation (HSCT) and the number of allogeneic HSCT (allo- HSCT) has increased signicantly. While invasive fungal infections (IFIs) remain major concerns in these patients, data regarding impact of these infections on mortality, length of hospital stay, and hospital charge are limited in the United States at a national level. Additionally, with many updates in transplant practice, risk factors for IFIs in these patients may have changed. Methods: To assess risk factors and impact of IFIs on mortality, length of hospital stay, and hospital charges, a quantitative and cross-sectional design was used to analyze secondary data from the 2010 Healthcare Cost and Utiliza- tion Project - Nationwide Inpatient Sample (HCUP NIS) database. Chi-square test, Mann-Whitney test, and multiple logistic regression were used for statistical analyses. Results: A total of 5,753 weighted hospital records of allo- HSCT were identied with a mean age of 44.8 19.1 years. The IFI rate was 7.8% (451), with aspergillosis (30.6%) and candidiasis (9.6%) as the two most common IFIs. Compared to patients without IFIs, patients with IFIs had nearly 5 times higher mortality (25.1% vs. 5.1%), longer hospital stays, and higher hospital charges (p < .01). Multiple regression ana- lyses on risk factors conrmed presence of graft-versus-host disease as a recognized risk factor for IFIs. However, younger age, female gender, and related donors were also identied as risk factors for IFIs in this analysis. The underlying reasons for these unexpected ndings will be explored. Conclusions: An analysis of a large U.S. inpatient database conrmed that allo-HSCT patients with IFIs have higher mortality and higher health care costs. The risk factors for IFIs have been identied that could enable better manage- ment and control of these infections. 332 The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Centers Analysis Jan Cerny 1 , Muthalagu Ramanathan 2 , Glen Raffel 3 , Natasha Fortier 4 , Lindsey Shanahan 4 , Tzafra Martin 5 , Laura Petrillo-Deluca 6 , Jayde Bednarik 7 , Rajneesh Nath 8 . 1 Division of Hematology/Oncology, University of Massachusetts, Worcester, MA; 2 Hematology/Oncology Section BMT, UMASS Memorial University Campus, Worcester, MA; 3 Hematology/Oncology Section BMT, UMass Medical Center, Worcester, MA; 4 Hematology/Oncology - BMT, UMass Memorial Medical Center, Worcester, MA; 5 Hematology/ Oncology Section BMT, UMass Memorial Medical Center, Worcester, MA; 6 Hematology/Oncology, UMass Memorial Medical Center, Worcester, MA; 7 Pharmacy, UMass Memorial Medical Center, Worcester, MA; 8 Hematology/Oncology, Section BMT, UMass Memorial Medical Center, Worcester, MA Background: ABO typing is not readily available within donor databases. ABO incompatibility between donor and recipient is not considered a hurdle to an allogeneic he- matopoietic stem cell transplantation (ALLOSCT). Conicting data still exist as to its inuence on graft-versus-host disease (GVHD), relapse, and survival. Method: We retrospectively examined the impact of ABO compatibility on outcomes of 109 patients who underwent matched unrelated donor (MUD), matched related (REL) and cord blood (CBU) ALLOSCT at our institution since 01/01/ 2010. Results: Median age was 58 years (range, 19.9- 83.6); 33 (30%) were female; 64 (59%) patients had a myeloid, 34 (31%) lymhoid, 8 (7%) plasma cell and 3 (3%) had other disorder; 57 (52%) patients received myeloablative, 25 (23%) non- myeloablative and 27 (25%) received reduced intensity con- ditioning. The stem cell sources were represented by 78 (72%) MUDs, 15 (14%) RELs and 16 (15%) CBUs. 80 (86%) of the MUD and REL transplants were 10/10, 11 (13%) were 9/10, 1 Abstracts / Biol Blood Marrow Transplant 20 (2014) S211eS256 S216

The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Center's Analysis

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Page 1: The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Center's Analysis

Abstracts / Biol Blood Marrow Transplant 20 (2014) S211eS256S216

challenge. Despite advances in allo-HSCT reducing risk ofmorbidity andmortality, relapse has not altered significantly.We performed a single institution review of relapsefollowing allo-HSCT in patients with AL examining salvagetherapy and characteristics of long term survivors.Methods: All adult patients who proceeded to an allo-HSCTfor AL from 1998-2012 (n¼100) were reviewed. 24 relapsedfollowing allo-HSCT and a detailed review of salvage treat-ments and outcomes was made. Probability of overall sur-vival (POS) and 95% confidence interval (CI) were calculatedby actuarial method.Results: The 5 year POS of the 100 patients with AL pro-ceeding to allo-HSCT was 71 % (CI 61-80%). Of 24 relapsingafter allo-HSCT, 17 had initial diagnosis AML, and 7 ALL. TheAML groupmedian agewas 49y (range 22-65), 53%male. Tenpatients received sibling donors, 6 unrelated donors and 1patient a related haplo-identical donor. Relapses weremostly systemic (14) and extra medullary (EM) 3 of the 17cases. Median time to relapse was 13 months (3-57). Salvagetreatments were: second allo-HSCT +/- chemotherapy(chemo) (n¼5); donor lymphocyte infusion (DLI) +/- chemo(n¼5); chemo +/- withdrawal of immunosuppression (WI)(n¼4); or palliative/supportive care (n¼3). Ten patients (57%)achieved complete response (CR), and CR was maintained by8 patients (47%), with a median follow up 34 months (range8-66). All deaths (n¼9) were due to disease. All 3 patientswith EM relapse are in ongoing remission.

In the ALL group (n¼7) median age was 22y (range 19-52), 57% of male. 3 were sibling donor transplants, 3 unre-lated and 1 patient received a double cord. Relapse wassystemic in 5 patients, and EM in 2. Median time to relapsewas 13 months (range 3-57). Salvage treatments comprised:chemo +/- WI (n¼3), second allo-HSCT +/- salvage chemo(n¼2), DLI +/- salvage chemo (n¼1), with 1 patient receivingnovel monoclonal antibody therapy. Three patients achieveda CR, however, all died, 2 of disease progression. Two patientsremain alive in PR with ongoing salvage treatment to bedetermined.Conclusions: Despite advances in allo-HSCT, long term sur-vival outcomes for patients with ALL who relapse after allo-HSCT remain poor. However, in contrast, for patients withAML who relapse, durable long-term remissions can beachieved with salvage therapy (with and without secondallo-HSCT) with almost half of our patients (47%) in ongoingCR at a median of 34 months (range 8-66). As shown in otherstudies EM relapse, may be salvaged with good long termresults.

331Impact of Invasive Fungal Infections on Mortality, Lengthof Hospital Stay, and Costs in Allogeneic HematopoieticStem Cell Transplant PatientsJenny Cai 1, Angela Prehn 2, Haran Schlamm3,Massimiliano Mucci 4, Aimee Ferraro 2. 1 Anti-infective/VaccineTA, Safety Evaluation and Reporting, Worldwide R&D, PfizerInc., Bridgewater, NJ; 2 2. Public Health Program, School ofHealth Sciences, Walden University, Minneapolis, MN; 3HTSPharma Consulting, LLC, New York, NY; 4 Anti-infective/VaccineTA, Safety Evaluation and Reporting, Worldwide R&D, PfizerInc., Milan, Italy

Background: Over the last decade, unrelated donors havebecome a vital resource for hematopoietic stem cell trans-plantation (HSCT) and the number of allogeneic HSCT (allo-HSCT) has increased significantly. While invasive fungalinfections (IFIs) remain major concerns in these patients,data regarding impact of these infections on mortality,

length of hospital stay, and hospital charge are limited in theUnited States at a national level. Additionally, with manyupdates in transplant practice, risk factors for IFIs in thesepatients may have changed.Methods: To assess risk factors and impact of IFIs onmortality, length of hospital stay, and hospital charges, aquantitative and cross-sectional design was used to analyzesecondary data from the 2010 Healthcare Cost and Utiliza-tion Project - Nationwide Inpatient Sample (HCUP NIS)database. Chi-square test, Mann-Whitney test, and multiplelogistic regression were used for statistical analyses.Results: A total of 5,753 weighted hospital records of allo-HSCT were identified with a mean age of 44.8 � 19.1 years.The IFI rate was 7.8% (451), with aspergillosis (30.6%) andcandidiasis (9.6%) as the two most common IFIs. Comparedto patients without IFIs, patients with IFIs had nearly 5 timeshigher mortality (25.1% vs. 5.1%), longer hospital stays, andhigher hospital charges (p < .01). Multiple regression ana-lyses on risk factors confirmed presence of graft-versus-hostdisease as a recognized risk factor for IFIs. However, youngerage, female gender, and related donors were also identifiedas risk factors for IFIs in this analysis. The underlying reasonsfor these unexpected findings will be explored.Conclusions: An analysis of a large U.S. inpatient databaseconfirmed that allo-HSCT patients with IFIs have highermortality and higher health care costs. The risk factors forIFIs have been identified that could enable better manage-ment and control of these infections.

332The Impact of ABO Incompatibility in Allogeneic StemCell Transplant (ALLOSCT): A Retrospective Single Center’sAnalysisJan Cerny 1, Muthalagu Ramanathan 2, Glen Raffel 3,Natasha Fortier 4, Lindsey Shanahan 4, Tzafra Martin 5,Laura Petrillo-Deluca 6, Jayde Bednarik 7, Rajneesh Nath 8.1 Division of Hematology/Oncology, University ofMassachusetts, Worcester, MA; 2Hematology/Oncology SectionBMT, UMASS Memorial University Campus, Worcester, MA;3Hematology/Oncology Section BMT, UMass Medical Center,Worcester, MA; 4Hematology/Oncology - BMT, UMassMemorial Medical Center, Worcester, MA; 5Hematology/Oncology Section BMT, UMass Memorial Medical Center,Worcester, MA; 6Hematology/Oncology, UMass MemorialMedical Center, Worcester, MA; 7 Pharmacy, UMass MemorialMedical Center, Worcester, MA; 8Hematology/Oncology,Section BMT, UMass Memorial Medical Center, Worcester, MA

Background: ABO typing is not readily available withindonor databases. ABO incompatibility between donor andrecipient is not considered a hurdle to an allogeneic he-matopoietic stem cell transplantation (ALLOSCT). Conflictingdata still exist as to its influence on graft-versus-host disease(GVHD), relapse, and survival.Method: We retrospectively examined the impact of ABOcompatibility on outcomes of 109 patients who underwentmatched unrelated donor (MUD), matched related (REL) andcord blood (CBU) ALLOSCT at our institution since 01/01/2010.Results: Median age was 58 years (range, 19.9- 83.6); 33(30%) were female; 64 (59%) patients had a myeloid, 34 (31%)lymhoid, 8 (7%) plasma cell and 3 (3%) had other disorder; 57(52%) patients received myeloablative, 25 (23%) non-myeloablative and 27 (25%) received reduced intensity con-ditioning. The stem cell sources were represented by 78(72%) MUDs,15 (14%) RELs and 16 (15%) CBUs. 80 (86%) of theMUD and REL transplants were 10/10, 11 (13%) were 9/10, 1

Page 2: The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Center's Analysis

Abstracts / Biol Blood Marrow Transplant 20 (2014) S211eS256 S217

(1%) 8/10, and 1 (1%) were 5/10 matched, 13 (80%) of CBUtransplants were 6/10 or higher match. 56 (52%) patientswere transplanted in CR1/PR1, 39 (36%) had stable disease or<PR and 13 (12%) had resistant or refractory disease. TheCMV status was 26 (25%) D-/R-; 40 (39%) D-/R+, 5 (5%) D+/R-and 32 (31%) D+/R+. 61 (56%) patients received ABOcompatible transplant, 26 (24%) had a minor incompatibilityand 22 (20%) had a major incompatibility.

The major ABO incompatibility group showed a trendtowards inferior survival compared to both ABO compatibleor minor ABO incompatible transplants. When evaluatingconditioning regimens separately similar trend was seenamong MA, NMA and RIC transplants, but did not reachstatistical significance.

No difference was seen in the following factors: gender,age at SCT, CMV status, acute or chronic GVHD.Conclusion: In our experience, the use of a major ABOincompatible donor may represent a risk factor for outcomeof ALLOSCT. Analysis of a larger cohort of patients may pro-vide further understanding of the impact of ABO compati-bility on ALLOSCT outcome.

333Myeloablative Conditioning Using IV Busulphan withPost Transplant Cyclophosphamide Is FeasibleMammen Chandy 1, Anupam Chakrapani 2, Sumit Goyal 3,Reena Nair 4, Vivek S. Radhakrishnan 5, Mita Roy Chowdhury 6.1 Director-TMC, and Head-Clinical Hematology & Bone Marrow

Table 1Mismatched Related Haplo e Identical SCT

UPN 11/2488 13/0765

Age(y)/ sex 29 / M 30 / MDiagnosis Relapsed AML CML - APDisease status Progressive diseases Progressive diseaseDonor Sister BrotherAge (y)/sex 33 / F 33 / MStem cell CD34+/kg 5.88 x 106 5.6 x 106

MNC/kg 4.33 x 108 5.3 x 108

engraftment D+14 D +17Mucositis Gr II Gr III/ IVGVHD - Gr IStay length 47 days 38 daysD+28 chimerism 100% 100%

status Alive +395 Died +60 DAH

Transplant, Tata Medical Center, Kolkata, India; 2 ClinicalHaematology & Bone Marrow Transplant, TMC, Kolkata, India;3 Tata medical Center, Kolkata, India; 4 Clinical Haematology,Tata Medical Center, Kolkata, India; 5 Clinical Hematology &Bone Marrow Transplant, Apollo Hospital, Bangalore, India;6 BMT Nursing, Tata medical Center, Kolkata, India

Five patients with progressive disease were transplantedusing the John’s Hopkins protocol but with IV busulphan3.2mg/kg/day x 4 days given along with fludarabine. Thedonors were all siblings and the graft was peripheral bloodstem cells harvested after 4 days of G-CSF. Table I gives thedetails of these patients.All patients had progressive disease and the patient withAML in first relapse with 30% blasts at the time of transplant(UPN 11/2488) is now one year post transplant with 100%donor chimerism and no graft versus host disease.. Theprotocol is well tolerated with rapid engraftment ( day +14-17), a very low incidence of mucositits and no VOD. Onepatient with CML and earlier blast transformation who hadreceived multiple rounds of chemotherapy and was inaccelerated phase at the time of transplant died of respira-tory failure with a presumptive diagnosis of Diffuse AlveolarHaemorrhage which could be related to busulphan. The pa-tient with progressive NK T cell lymphoma who had failedCHOP, and SMILE rejected his graft after achieving full donorchimerism and succumbed to sepsis with multi-organ failurewhile pancytopenic.The addition of myelablationwith IV busulphan to the John’sHopkins protocol of PT-Cy is feasible and may reduce thefrequency of relapse.

334Phase II Trial of Reduced Intensity Busulfan / ClofarabineConditioning with Allogeneic Hematopoietic Stem CellTransplantation for Patients with AML, MDS, and ALLYi-Bin Chen 1, Shuli Li 2, Candice Del Rio 3, Erin Coughlin 1,Karen K. Ballen 1, Corey S. Cutler 4, Bimalangshu R. Dey 3,Vincent T. Ho 5, Steven L. McAfee 6, Thomas R. Spitzer 7,Edwin P. Alyea III 8. 1Massachusetts General Hospital, Boston,MA; 2 Biostatistics, Dana-Farber Cancer Institute, Boston, MA;3 Bone Marrow Transplant Unit, Massachusetts GeneralHospital, Boston, MA; 4Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; 5Dana Farber CancerInstitute, Boston, MA; 6 BMT Program, Dept of Medicine,Massachusetts General Hospital, Boston, MA; 7 Bone MarrowTransplantation Unit, Massachusetts General Hospital, Boston,MA; 8Dana-Farber Cancer Institute, Boston, MA

11/4498 13/2892 12/4018

26 / M 35 / M 25 / FCML - AP NK Cell Lymphoma PCLProgressive disease Progressive disease Progressive diseaseBrother Brother Brother27 / M 38 / M 32 / M2.24 x 106 5.7 x 106 8.0 x 106

3.46 x 108 12.4 x 108 6.72 x 108

D +15 - D +14Gr I Gr IV Gr III

-27 days 36 days 28 days93% 99.9% (11/09)

64.3% (17/09)99.8%

Alive +60 Died Alive