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Hematologic Malignancy for Internist 2014. Chinadol Wanitpongpun MD. Cancer treatment. Chemotherapy & Targeted therapy Radiotherapy Surgery Other : Bone Marrow transplantation (BMT) / Tumor vaccine. BSA. BSA = √Ht X BW /3600 Actual BW (JCO2012) Overweight (conditioning regimens) - PowerPoint PPT Presentation
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Hematologic Malignancy for Internist 2014
Chinadol Wanitpongpun MD.
Cancer treatment
Chemotherapy & Targeted therapy Radiotherapy Surgery Other : Bone Marrow transplantation
(BMT) / Tumor vaccine
BSA
BSA = √Ht X BW /3600 Actual BW (JCO2012) Overweight (conditioning regimens)
Actual > 40% IDW : Adjust BW Adjust BW = IBW + 0.5(Actual-Ideal)
Male 50 + 2.3 X (inch > 60) Female 45 + 2.3 X (inch > 60)
Hematologic Malignancy
Myeloid Neoplasms Lymphoid Neoplasms Histiocytic & Dendritic neoplasms
The Must Known
Acute Leukemia especially M3 MPNs : PV / ET / CML / AMM Lymphoma : HD / DLBCL / BL Multiple Myeloma
Scope for each Diseases
Criteria Diagnosis Clinical features or manifestations Classification Staging Prognostic score Treatment
Myeloid Neoplasms
Myeloid Neoplasms
Differentiation Maturation
Proliferation Disease
AbsentDysplasiaDysplasiaNormal
IncreaseNormalIncreaseIncrease
AMLMDS
CMMoLMPNs
AML (1)
FAB classification : morphology M0-M7 WHO classification : cytogenetic Acute marrow failure within 8 weeks Hepatosplenomegaly rare in de novo WBC usually high (leukemic profile) except
aleukemic or hypoplastic leukemia
AML (2)
Diagnosis by
Blast > 20% in PBS and BM
except t(8;21) / t(15;17) / inv(16)
t(16;16) or erythroleukemia
Flow cytometry : blast gate >20%
M0-M7 by CD marker
Mass biopsy : Granulocytic sarcoma DDX : ALL
AML-M6
2 forms Pure erythroid leukemia
Erythroid > 80% minimal myeloblast Acute erythroid/myeloid leukemia
Erythroid > 50% Blast > 20% of all non erythroid cell
Flow Cytometry for AML
1. Blast gate : Acute Leukemia
2. AML / ALL : MPO / TdT / CD19 /
CD 34 / CD117
3. M3 / Non M3 : CD34 - & HLADR –
4. M6 (GPA) / M7 (CD41/61)
5. M4/M5 (CD11c / CD14 / CD64)
6. M0-2 (MPO / CD15) -/-, +/-, +/+
Feature AML ALL
IncidenceMean ageL+S+LN+Special organ
80%Any40%
CNS (M4 or M5)Gum / Skin (M5)Hypokalemia M5Chloromas (M2)
DIC (M3)
20%20-30 (<50)
50%CNS JointTestis
Mediastinum (ATLL and LBL)
AML (3)
AML (4)
Myeloblast Lymphoblast
Size 3-5X RBCLow N:C ratio
Blue-gray cytoplasm3-5 Nucleoli
Granule present Auer rod or Faggot
MPO + / TDT-
Size < 3X RBCHigh N:C ratio
Blue-purple cytoplasm0-2 Nucleoli
Granule absentAbsent
MPO- / TDT+
AML (5)
ALL
Cytogenetic in AML
Normal Cytogenetic AML
AML (6)
AML (7)
Mutation associated with prognosis Favorable + c-kit mutation = intermediate Normal karyotype + NPM1 = favorable Normal karyotype + CEBPA = favorable Normal karyotype + FLT3/ITD = unfavorable
AML (8)
Treatment 2 phases Induction : 3+7 regimen
(Idarubicin 3 + Ara-C 7) Post remission therapy or consolidation
depend on cytogenetic
Favorable : CMT (HDAC 3-4 cycles)
Intermediate / Unfavorable : ALBMT
Cytarabine (Ara-C) SE
Neutrophilic Eccrine Hydradenitis Pyoderma Gangrnosum Keratitis / Conjunctivitis Cytarabine syndrome : seizure &
cerebellar toxicity
APL (1)
Acute promyelocytic leukemia Abnormal promyelocyte
APL (2)
Present with bleeding (DIC) or BM failure
Diagnosis by PBS / BMA Abnormal promyelocyte or blast > 30% 2 subtypes
Hypergranular or Typical : Low WBC Hypogranular (Microgranular) : High WBC
APL (3)
APL (4)
Flow cytometry dual low or absence expression of HLA-DR and CD34 and bright expression of CD33
Cytogenetic : t(15;17) Other : t(5;17) or t(11;17) poor response
to ATRA just only t(11;17) associated PLZF-RARA
APL (5)
Treatment APL with PLZF-RARA treat as AML non M3
3 phases Induction : Idarubicin + ATRA Consolidation
1st and 3rd cycle : Idarubicin + ATRA + Ara-C 2nd cycle : Idarubicin + Mitoxanthone
Maintenance : 6-MP + MTX + ATRA 2 yr.
Ara-C in Consolidation
Depend on risk group High risk
Initial WBC > 10,000 Initial Platelet < 40,000
APL (6)
ATRA side effects Differentiation syndrome : fever + weight
gain + dyspnea + pleural effusion and ascites + leukocytosis
treat by stop ATRA + IV steroid Hepatitis Pseudotumor cerebri Dry mouth
APL (7)
ATO3 SE as ATRA QTc prolong Hypokalemia / Hypomagnesemia
MDS (1)
Subacute to chronic cytopenia Elderly 80% involve erythroid (anemia) No organomegaly Dysplastic features > 10% of lineage Diagnosis by PBS + BMA + Chromosome
DDX. Erythroid Hyperplasia
Acute Blood loss Hemolysis Megaloblastic anemia Myelodysplastic syndrome (MDS) AML-M6
MDS (2)
Dysplastic features Erythroid : nucleus-multiple / budding
Ring sideroblast (>15% erythroid series) Myeloid : bilobed / Pelger-Huet
Incease myeloblast Megakaryocyte : micro-hypolobated
Cellularity mostly increase with eythroid hyperplasia
MDS (3)
WHO Classification RA / RCMD + RS RN / RT 5q- syndrome RAEB-I / RA EB-II MDS/MPD AML Unclassified
MDS (5)
Treatment Transfusion / Iron chelation 5q- syndrome : lenalidomide RR 67% Hypoplastic / HLADR-15 / PNH : treat as AA RN / RT : hypomethylating agent IPSS score
Low risk : Growth factors EPO + G-CSF High risk : BMT / Hypomethylating agent
Predictive Factor for EPO resp.
EPO level > 200 (500) U/L RBC Transfusion > 2 units/month
0 RR 74%
1 RR 23%
2 RR 7% IPSS score / RAEB / Cytogenetic
CMMoL
Chronic myelomonocytic Leukemia Persistent of PBS monocytosis > 1,000 Ph chromosome negative Dysplastic change and blast < 20% Most common presentation :
leukocytosis / splenomegaly / arthralgia Treatment : supportive or cytoreductive
Thrombophilia both A. & V.
DDX (5) Antiphospholipid syndrome Hyperhomocysteinemia Heparin induced thrombocytopenia (HIT) Myeloproliferative neoplasm (MPD) Dysfibrinogenemia
Polycythemia Vera (1)
Present with arterial and venous thrombosis / headache or dizziness / post bathing pruritus / erythromelagia / splenomegaly / gout / (false PT/PTT prolong)
20% turn AMM / AML and death Awareness in Low MCV with Normal Hb Diagnostic criteria
2 major + 1 minor or first major + 2 minor
PV (2)
Major criteria Hb > 18.5 in men and 16.5 in women or 17 / 15 +
sustain increase Hb2 g/dl /RBC mass >25% NPV JAK2 V617F mutation (95%)or other ex. exon12
Minor criteria BM : panmyelosis Low EPO level In vitro endogenous erythroid colony formation
PV (3)
Polycythemia Vera Reactive Erythrocytosis
Insidious onsetThrombohemorrhagic
ErythromelagiaPost bathing pruritus
Absent causes Splenomegaly
JAK2 V617F 95%
Acute / abrupt onsetAbsent Absent AbsentPresent Absent
Negative
PV (4)
Reactive setting Tissue hypoxia
Cyanotic heart disease Lung disease : COPD Abnormal Hb : CO / Met / Tak
EPO producing tumor Renal artery stenosis Therapy related : EPO / Androgen
PV (5)
Treatment ASA in all patients if no contraindicated and
effective for treatment erythromelagia Cytoreductive in high risk
Age > 60 yr. /previous thrombosis CAD risk or Platelet > 1,500,000
Blood letting keep Hct < 45 in men and 42 in women and 39 in pregnancy
PV (6)
Cytoreductive agents Hydroxyurea Interferon : young patient or pregnancy
Caution
Hydroxyurea combination with ddc / AZT / indinavir show median decline in CD4 approximately 100/mm3
Increase risk peripheral neuropathy / hepatotoxicity and pancreatitis in ddc / AZT
Megaloblastoid change RBC
Essential Thrombocytosis (ET)
Thrombocytosis Thrombosis > hemorrhage JAK2 V617F + 50% Normal life expectancy / mild S++ Diagnostic criteria
4 of all Platelet > 450,000 + BMBX high MK
+ R/O other MPN + JAK2 or no reactive cause
ET (2)
ET Reactive
ThrombosisHemorrhageInsidious onset No causesMay be splenomegaly
Absent Absent Acute / Abrupt Present causesAbsent
ET (3)
Reactive thrombocytosis Iron deficiency anemia Splenectomy Hemolysis or bleeding Infection or inflammation Tissue damage Malignancy Rebound phenomenon
ET (4)
Treatment ASA in high risk or CAD risk Cytoreductive in high risk
Hydroxyure Analgrelide
No blood letting Pregnancy : IFN-α
Chronic Myeloid Leukemia (1)
Pluripotent stem cell disorder Philadelphia or Bcr-Abl + 100% Most common p210 KD chimeric fusion
protein p190 KD in Ph+ ALL / p230 KD in CNL Leukocytosis relate with spleen size DDX : other MPN and CNL
CML (2)
CML Leukemoid reaction
Hyperviscosity-priapismLeukemic infiltration
Insidious onsetNo causes
SplenomegalyPlatelet / Basophil / Eo
PBS:Blast-promyelocytePhiladelphia + / LAP low
AbsentAbsent
Acute Onset Severe stress / Sepsis
AbsentNormal
Left shift Absent / LAP high
CML (3)
Chronic Neutrophilic Leukemia (CNL) WBC > 25,000 Segmented PMN + Band > 80% Myeloblast < 1 % Immature granulocyte < 10% Hepatosplenomegaly No causes Ph negative
CML (4)
Chronic Accelerated Blastic
Blast < 5-10% Basophil < 20%Response to TKI
Blast 10-19%Basophil > 20%Persist Plt↑ or ↓Progressive S++Increase WBC Clonal evolution
Blast > 20%Any BMX : cluster of blast Extramedullary blast prol.
DDX
CML -BP Ph+ AML
Previous history SplenomegalyPlatelet normalBasophiliaEosinophiliaPh+ t(9;22)Bcr-Abl 210 kD
AbsentRareAlmost always decrease AbsentAbsentPh+ t(9;22)Bcr-Abl 190 kD
CML (5)
Treatment CP : Imatinib 400 mg/day / Nilotinib /
Dasatinib AP : Imatinib 600-800 mg/day / N / D BP : Imatinib 600-800 mg /day or D /
CMT then Allogeneic BMT Evaluate response and F/U follow by
milestone
Treatment Failure
Poor Adherence / Compliance Overproduction Bcr-Abl Alternative TK pathway Mutation analysis
ELN 2013
Time Optimal Warning Failure
3 mo. Bcr < 10%Ph+ < 65%
>10% 65-95%
No CHR> 95% / M
6 mo. Ph+ < 35% Ph+ 35-65 Ph+ > 65%
12 mo. Bcr < 1 %Ph+ 0
1-10 %Ph+ 1-35%
>10% >35% / M
Any time > MMR CCA/Ph-7 -7q Bcris>0.1%
Loss CHRLoss CCyRMMR / M
Primary Myelofibrosis (PMF)
Or Agnogenic myeloid metaplasia MK and Histiocyte proliferation
PDGF and FGF fibroblast Mean age : 60 yr. Present with anemia and splenomegaly Osteosclerosis / Portal HT-EV JAK2 + 50%
PMF (2)
Diagnostic criteria : all major + 2 minor Major : BM change + R/O other MPN +
clonal marker Minor : PBS + increase LDH + anemia + S+
Prognostic score : Lille score Treatment
Allogeneic BMT / JAKII inh.(Ruxolitinib) Supportive / HU / Splenic RT / Transfusion
Conclusion MPNs
PV ET CML AMMElderly PolycythemiaS+ThrombosisPanmyelosisJAK2 V617FJAK2 exon12ASAHU / IFNBlood letting
ElderlyThrombocytosisS+ or S-ThrombosisIncrease MKJAK2 V617FMPLW151L/KASAHU / IFN Analgrelide
Yound adultLeukocytosisS++ WBCSplenomegalyHigh M:E Philadelphiat(9;22)TKIBMT
ElderlyAnemiaS++ HbAnemiaDry tapJAK2MPLBMT HU / JAKISupportive
Lymphoid Neoplasms
Lymphoid Neoplasms
Precursor : Acute Lymphoblastic Leukemia (ALL) Lymphoblastic lymphoma (LBL)
Mature : Lymphoma
ALL (1)
20% of adult leukemia Acute BM failure Tissue infiltrate : CNS / testis Mediastinal mass in ATLL / T-LBL Poor prognosis in adult 5yr. OS 30% Diagnosis by flow cytometry and BMA
ALL (2)
Risk classification Ultrahigh risk : Ph+ High risk : 1 of all following
Age > 35 or Poor PS WBC > 30,000 in B 100,000 in T Pro-B CD10- / Early and mature T Cytogenetic : t(4;11) / -7 / +8 / 11q23 / t(1;19) / hypoploidy CR after 4 wk. or MRD + > 0.01%
Standard risk : negative above marker
ALL (3)
Treatment Ultrahigh risk and high risk
Induction to CR then Allogeneic BMT Standard risk
ALL protocol or HyperCVAD regimen + upfront BMT
Lymphoma
Hodgkin Lymphoma Non Hodgkin Lymphoma
Nodal presentationCLN / Mediastinal LN Contiguous LN involveAlcoholic induced pain
Pel-Epstein feverBM involvement 15%Reed-Sternburg cell
Nodal or ExtranodalAny area
Skip lesion Absent
B symptomBM involvement 30%
Absent
Hodgkin Lymphoma (1)
Classical HD 95% Nodular sclerosis 70%
Young female / CLN & mediastinal mass / limited
Mixed cellularity Advanced stage / splenic involvement 60%
Lymphocyte –rich elderly present with advanced Lymphocyte-depletion elderly associated HIV
Nodular lymphocyte predominance HD 5%
HL (2)
Staging by Ann Arbor Prognostic score
Stage I-II : favorable risk score Stage III-IV : IPS score
Treatment for CHL I/II : ABVD X4 + IFRT (2+20 / 4+30) III/IV : ABVD X6-8 + IFRT / ESC BEACOPP NLPHD : RT / R / Observe
NHL (1)
B cell Lymphoma T cell lymphoma
PCNSL / IVL / PHL / BoneTesticular involvementImmunologic phenomenaLess commonLung : LN / nodule (LG) M protein IHC : CD20 / 79a / CD138
Skin / other extranodalRare except in NK-T cellLess commonLeukopenia / HPSLung : interstitial infiltrateAbsent except AITLIHC : CD3 / CD45Ro
NHL (2)
Indolent Lymphoma Aggressive Lymphoma
Insidious onset > 6 mo.Slow progressive in sizeWaxes and wanes No or Late B symptomAbsent / Low Ki-67Low or High normal LDHMostly involve BM Difficult to cure
Acute-Subacute in 6 mo.Rapid progressive in sizeAbsentAt presentation Tumor lysis syndromeHigh LDHAbout 30% Cure or Die
NHL (3)
Lymphoma in Thailand HD 15-20% NHL 80-85%
B cell 90% DLBCL 35% FL 30% MCL 10% MALT 10% / CLL 10% Others 5%
T cell 10% PTCL NOS 30% + AITL 20% and other
B-cell Lymphoma
Indolent Aggressive Very Aggressive
CLL / SLLHCLMZLFL
LPL
DLBCLPCNSLPMBL
IVLLG
PBLPELMMMCL
LBLBL
PCL
Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
CLL (leukemia) / SLL (lymphoma) Same IHC but difference presentation Asymptomatic / LN++ / L+S+ AIHA / ITP / CIDP M protein maybe found / HypoGammaGlb Absolute lymphocytosis > 5,000 Flow : + CD5 / CD23 and – FMC7
CLL/SLL Treatment
SLL stage I : IFRT SLL stage II-IV / CLL stage 0-2 : Ind
Organ dysfunction / Bulky disease Anemia / Thrombocytopenia not resp. steroid Lymphocyte doubling < 6 mo.
CLL stage III-IV or Binet C FCR / R-CHOP / R-CVP R / R + alkylating agent
Hairy cell Leukemia (HCL)
Elderly present with splenomegaly and pancytopenia with monocytopenia
PBS : lymphocyte with cytoplasmic hairy projection
BMA : dry tap (myelofibrosis) BMBX : fried-egg appearance IHC : CD5- CD23- / + Cd11C,25,103,
TRAP and Annexin A1
HCL Treatment
Indication for treatment Systemic symptom / Splenic discomfort Hb < 12 / ANC < 1,000 / Plt < 100,000 Recurrent infection
Regimen Cladribine / Pentostatin CHOP / CVP R / IFN
Marginal zone Lymphoma (MZL)
Nodal : LN ++ MALT
Gastric (ulcer in stomach) ass. H. pylori Non gastric MALT
Orbital (mass) ass. C. psiitaci Thyroid (mass) ass. Hashimoto’s thyroiditis Salivary gland (mass) ass. Sjogren syndrome
Splenic MZL (s+++) ass. HCV infection
MZL Treatment
Nodal : treat as FL Splenic MZL
Asymptomatic : observe Symptomatic : treat HCV / Splenectomy / R
MALT Gastric : I/II : H.p / R / RT, III-IV : Ind
R-CHOP / R-CVP
Non Gastric : I/II : Local RT, III-IV as FL
Follicular Lymphoma (FL)
Elderly in 6th decade LN ++ / S++ Skin / GI tract- duodenum / Ocular / Breast 40-70% BM involvement IHC : + CD10 and BCL6 /t(14;18)
FL Treatment
Grade III : treat as DLBCL I-II Stage Ia/IIa : IFRT + R Stage IIb-IV : Indication :
Organ dysfunction Cytopenia / Bulky disease / Compressive symptom Regimen : R-CHOP / R-CVP + R maintenance 2 yr.
Lymphoplasmacytic Lymphoma / Waldenstrom Macroglobulinemia
Median age 60 yr. Associated genetic or HCV infection IgM production >> IgG >>>>IgA 30% present with hyperviscosity synd. AIHA or Cryoglobulinemia Diarrhea and coagulopathy BX : Dutcher bodies
LPL Treatment
Indication for treatment As other indolent Cold agglutinin disease Cryoglobulinemia Amyloidosis Hyperviscosity
Regimen R-CHOP / R-CVP
Flow cytometry
Disease CD5 CD23 Other
CLL/SLLMCLFLLPLMZLHCL
++----
+-----
FMC7-CCD1+CD10+ 60%CD138t(11;18)CD11c/25/103/AXA1
Conclusion Treatment of Indolent Lymphoma
Followed by stage / prognosis score and indication for treatment
Wait and watch Radiation Chemotherapy
DLBCL (1)
Most common NHL subtype Nodal or extranodal mass 11-27% BM involvement
Discordant > concordant Nucleus > macrophage or > 2X Lymphocyte Staging by Ann arbor Prognostic score : IPI
DLBCL (2)
Treatment Stage I-II IPI = 0 : R-CHOP 3 + RT or 6 cycles Stage I-II IPI > 1 or stage III-IV
R-CHOP 6-8 cycles + RT in bulky lesion
CNs prophylaxis in testicular and sinonasal / high LDH / > 1 extranodal site / extensive BM involvement / Breast / IOL / Paraspinal / HIV
RT : Compression-X / CNS/SN/BR/PS/T/W G-CSF prophylaxis : >60 / BM / Malnut / ECOG > 2
Primary CNS Lymphoma
Almost all DLBCL in CNS without evidence of systemic disease
Intracerebral or intraocular mass Supratentorial homogenous lesion 90% intraocular lesion develop
contralateral tumor Treatment : high dose MTX regimen +
RT + IT CMT
PCNSL Treatment
ECOG > 2 : Palliative care / WBRT ECOG 0-2
< 60 yr : HDMTX + HDAC + RT + IT >60 yr : HDMTX + RT + IT
Primary Mediastinal LBCL
Young adult female DLBCL in mediastinum Absent other LN and BM DDX : Nodular sclerosis HL / LBL /
ALCL / BL and ATLL Treatment :
PMBL Treatment
Stage Ia / IIa R-CHOP + RT R-ICE + RT
Stage IIb/IIx / III-IV R-CHOP DA-EOPOCHR
Intravascular Lymphoma (IVL)
Selective growth within vessels 2 forms Western form : neurocutaneous Asian form : multiple organ failure / L+S+
pancytopenia / hemophagocytic synd. Diagnosis by skin biopsy Poor prognosis
Lymphomatoid Granulomatosis
Rare 90% pulmonary involvement Other : brain / kidney / liver and skin Rare LN and BM involvement CXR : vary in size multiple pulmonary
nodule Poor prognosis
Plasmablastic Lymphoma
High incidence in HIV patient Present with oral cavity mass Associated with EBV infection 100%
Primary Effusion Lymphoma
Lymphoma that present with effusion without tumor mass
Pleural / pericardial and ascites Associated with HHV8 in HIV patient
Infection and Lymphoma
H. pylori : Gastric MALT C. psittaci : Orbital MALT HCV : Splenic MZL HTLV1 : ATLL HHV8 : PEL EBV : PBL / BL / NKT / PCNSL etc. HIV : distinct clinical course
Multiple Myeloma (1)
Clonal plasma cell disorder Clinical manifestation
Chronic anemia or BM failure Bone pain / osteoporosis / compression fracture Mass with compressive symptom Hyperviscosity syndrome Hypercalcemia and renal failure Amyloidosis : IgA / λ light chain
MM (2)
Classification MGUS Smoldering Symptomatic MM Non secretory MM : no M protein Solitary / extraosseous plasmacytoma Plasma cell leukemia : > 2,000 or 20% AL amyloidosis POEMS
MM (3)
Diagnosis all of 3 criteria M protein (except non secretory MM)
SPEP or SFLCR
BM plasma cell > 10% or plasmacytoma CRAB or related organ / tissue impairment
Ca > 11.5 / Hb < 10 / Cr > 2 Bone : osteolytic / severe osteopenia / fracture
Normal ALP no osteoblastic activity except IgD type
Recurrent infection / Hyperviscosity / Amyloidosis
MM (4)
Common type : IgG > Light chain / IgA > >> IgD / IgE / IgM / biclonal MM
SPEP negative can’t be R/O MM should be evaluate SFLCR / IF
SFLCR (κ/λ ratio) normal 0.26-1.65 If out of proportion : light chain disease
Immunofixation PBS : Rouleaux formation
MM (5)
Staging by ISS B2microGb Alb Stage I < 3.5 > 3.5 Stage II Nor I or III Stage III > 5.5 Any
Predict median survival 60 / 45 / 30 mo. Risk classification by cytogenetic
MM (6)
Treatment (8) Chemotherapy
Transplant candidate Bortezomib (velcade ) based : Vel-Dex X 4
then Autologous BMT + consol / M Non transplant candidate
Any regimen ex.VMP until best response + 2 + consolidation & maintenance therapy
MM (7)
Transplantation Bisphosphonate EPO : Disease status at least VGPR Infectious prophylaxis : PCP / HZV
+ vaccine Pneumococcal / IF / HIB Thromboprophylaxis : Thal / Len Radiation prevent fracture Tumor vaccine
Mantle cell Lymphoma (MCL)
Aggressive form Lymphomatous polyposis of large bowel Flow : + CD5 / FMC7 and –CD23 Cyclin-D1 positive ass. t(11;14) Treatment
MCL Treatment
Stage I/II : CMT alone R-CHOP / R-HyperCVAD / CALGB
Stage III-IV : R-CHOP / R-HyperCVAD Trasnplant candidate : Autologous BMT Non transplant candidate : + R maintenance
Burkitt Lymphoma
Short doubling time tumor Tumor lysis syndrome Distal ileum and cecal mass / testis Most common translocation : t(8;14)
Associated with c-myc gene Treatment :
Low risk : CODOX-M X 3 cycles High risk : CODOX/IVAC or HyperCVAD 8 cycle
Low risk Burkitt
All of these criteria Completely resected abdominal lesion or
single extraabdominal lesion < 10 cm. Normal LDH
T-cell Lymphoma
Extranodal Nodal Cutaneous
NKTCLETCL
HSTCL
ALCLAITL
PTCL, NOS
MF & SSSPLTCL
Leukemic presentation of TCL : PLL / ATLL / LGL
Extranodal NK/T cell Lymphoma, nasal type
Lethal midline granuloma Strongly EBV association Mass in NP and Paranasal sinus CD56 and CD45Ro + Treatment : Radiosensitive
CHOP is not enough
Highly expression P-glycoprotein
Efflux CMT esp. Doxorubicin
ENNKTCL, Nasal type TX
Extranasal / Nasal stage III-IV Systemic CMT : SMILE / AspaMetDex Autologous BMT
Nasal stage I without risk factor : RT alone Nasal stage I with risk factor /II
CCRT or Sequential CMT + RT
Enteropathic T cell lymphoma
Associated celiac disease Most commonly in jejunum or ileum Present with intestinal perforation Chronic diarrhea with malabsorption Treatment : CHOP or EPOCH
γδ-Hepatosplenic T cell Lymphoma
Young adult male 20% arise in pt. with long term
immunosuppressive drug for solid organ transplant
L+++S++ Aggressive and poor prognosis
Anaplastic Large cell (ALCL)
ALK + good prognosis Treatment : CHOP
Angioimmunoblastic (AITL)
Generalized LN++ / L+S+ Systemic symptom Polyclonal gammopathy Pleural effusion / arthritis / ascites Cold agglutinin disease RF + Anti-SMA + Treatment : CHOP / EPOCH
PTCL, NOS
Nodal form Not compatible with AITL / ALCL Advanced disease Paraneoplastic : eosinophilia / pruritus
and hemophagocytic syndrome Treatment : CHOP / EPOCH + BMT
Mycosis Fungoides (MF) and Sezary syndrome
Most common cutaneous T cell lymphoma Limited to skin with wide spread Skin lesion : patch / plaque or tumor Intraepidermal collection of cell
(Pautrier abscess) Treatment : PUVA / CSA / CMT
SCPLTCL
Subcutaneous paniculitis 20% associated SLE Present with multiple subcutaneous nodule
on extremities and trunk May cytopenia / hepatitis / HPS Hepatosplenomegaly
ATLL
HTLV-1 associated Acute variant
High WBC / rash / LN++ / hypercalcemia T cell impairment OI
Lymphomatous variant LN ++
Chronic variant Exfolliative skin rash
Large granular lymphocytic leukemia (LGL)
Associated AI disease : RA Persistent LGL 2,000 > 6 mo. Neutropenia Hypergammaglobulinemia
Conclusion TX T-NHL
CMT CHOP is not enough except ALK+ ALCL CHOEP / EPOCH / CEOP NK-T : SMILE / AspaMetDex
RT esp. NKT If possible : BMT in all patients
Except easily controlled Cutaneous form and ALK+ ALCL
Common sites of Lymphoma (1)
CNS : DLBCL Orbital : MALT / FL / DLBCL Sinus : DLBCL / NKT Oral cavity : PBL Testis : DLBCL / BL / LBL / NK Lung : LG Mediastinum : NS / PMBL / ALCL /
T-LBL / BL
Common sites of Lymphoma (2)
GI tract Stomach : MALT / DLBCL Duodenum : FL / DLBCL Jejunum : ETCL / IPSID / DLBCL Ileum : BL / DLBCL Colon : MCL / DLBCL
Effusion : PEL
The Must Known
Acute Leukemia especially M3 MPNs : PV / ET / CML / AMM Lymphoma : HD / DLBCL / BL Multiple Myeloma
Question and Answer
THE END