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