A CASE OF ACUTE A CASE OF ACUTE MYELOID MYELOID LEUKEMIALEUKEMIA

PROF S SHIVAKUMARPROF S SHIVAKUMAR

P SENTHIL KUMAR MD PGP SENTHIL KUMAR MD PG

Rajendran Rajendran 42 yrs/ M42 yrs/ M c/oc/o

Multiple swellings in the neck and Multiple swellings in the neck and submandibular regionsubmandibular region

Fever Fever Breathlessness Breathlessness

3months3months Pain abdomenPain abdomen Loss of appetite/ Loss of wt.Loss of appetite/ Loss of wt. No cough with sputumNo cough with sputum No dysuria, rashes, jaundiceNo dysuria, rashes, jaundice Bowel and bladder - N Bowel and bladder - N

Past H/oPast H/o No DM/ HTN/ IHD/ PT/ BA/ STROKENo DM/ HTN/ IHD/ PT/ BA/ STROKE

Personal H/oPersonal H/o Smoker/ alcoholicSmoker/ alcoholic Agricultural workerAgricultural worker

Family H/oFamily H/o Nil Nil

Treatment H/oTreatment H/o Pt on ATT for PL effusion past 3 monthsPt on ATT for PL effusion past 3 months

O/EO/E ConsciousConscious OrientedOriented FebrileFebrile Pallor +Pallor + Clubbing+Clubbing+ Subconjunctival hemorrhageSubconjunctival hemorrhage Submandibular/ cervical / supraclavicular Submandibular/ cervical / supraclavicular

LN +LN + No icterus/ cyanosis/ PE/ JVP.No icterus/ cyanosis/ PE/ JVP.

RSRS BS BS Lt mamary/ infra Lt mamary/ infra

axillary/ axillary/ infrascapular areasinfrascapular areas

Stony dullnessStony dullness Chest wall movements Lt sideChest wall movements Lt side

CVSCVS S1 S2 +S1 S2 + No murmurNo murmur

ABDABD No organomegalyNo organomegaly No FFNo FF

LABLAB HemogramHemogram

HbHb - - 5.65.6 g/dl g/dl TLCTLC -- 30,10030,100/cu mm/cu mm DCDC -- blast 60%blast 60% P24 L 04 P24 L 04

Myelocyte 12Myelocyte 12 Platlets Platlets - - 20.00020.000/ cu mm/ cu mm RBC RBC - - 1.6 million/ cu mm1.6 million/ cu mm PCVPCV - - 15 %15 %

PERIPHERAL SMEARPERIPHERAL SMEAR RBC RBC -- Normochromic Normocytes Normochromic Normocytes

and few hypochromic microcytes.and few hypochromic microcytes.

-- No hemoparasites seen No hemoparasites seen

WBCWBC -- Count increased with Count increased with BLASTS BLASTS showing occasional showing occasional Auer RodsAuer Rods..

PLATLETS-PLATLETS- DiminishedDiminished

BONE MARROWBONE MARROW HypercellularHypercellular Marrow replaced by Marrow replaced by

Leukemic cells with Leukemic cells with BLAST BLAST showing showing MYELOID MONOCYTICMYELOID MONOCYTIC differentiation up to differentiation up to 70 %70 %

ERYTHROPOIESIS ERYTHROPOIESIS MEGAKARYOPOIESISMEGAKARYOPOIESIS CYTOCHEMISTRYCYTOCHEMISTRY

MPOMPO -- InconclusiveInconclusive PASPAS -- NegNeg

RFTRFT UreaUrea -- 32 mg/dl32 mg/dl CreatinineCreatinine -- 0.8 mg/dl0.8 mg/dl

Bl sugarBl sugar -- 105 mg/dl105 mg/dl LFTLFT

TBTB -- 0.7 mg/dl0.7 mg/dl DBDB -- 0.3 mg/ dl0.3 mg/ dl SGOTSGOT -- 24 Iu/L24 Iu/L SGPTSGPT -- 22 Iu/L22 Iu/L SAPSAP -- 1O5 Iu/L1O5 Iu/L

CXRCXR -- Lt pleural effusionLt pleural effusion ECGECG -- WNLWNL USG ABDUSG ABD -- Lt pleural effusionLt pleural effusion

- - LIVER/ SPLEEN LIVER/ SPLEEN normalnormal

SPUTUMSPUTUM AFBAFB -- NegNeg Grams stainGrams stain -- NegNeg Malig cellsMalig cells -- NegNeg

Pleural FluidPleural Fluid ProteinProtein -- 4.6 g/dl4.6 g/dl SugarSugar - - 84 mg/dl84 mg/dl WBCWBC -- 26002600/ cu mm / cu mm

( P 11 L 39 )( P 11 L 39 ) RBCRBC -- 30,00030,000/cu mm/cu mm SmearSmear -- +ve for MALIGNANT +ve for MALIGNANT

CELLSCELLS Grams stainGrams stain -- No organismsNo organisms AFBAFB -- NegNeg

Problems Problems

FeverFever LymphadenopathyLymphadenopathy Pleural effusionPleural effusion Subconjunctival hemorrhageSubconjunctival hemorrhage Loss of wtLoss of wt

DIAGNOSISDIAGNOSIS

ACUTE MYELOID LEUKEMIA ACUTE MYELOID LEUKEMIA – M4 WITH MALIGNANT – M4 WITH MALIGNANT PLEURAL EFFUSION PLEURAL EFFUSION

ACUTE ACUTE MYELOID MYELOID LEUKEMIALEUKEMIA

ETIIOLOGYETIIOLOGY HEREDITYHEREDITY - - Downs , Klinefelters, Downs , Klinefelters,

patau, patau, Chromosomal breakage Chromosomal breakage syndromessyndromes

RADIATIONRADIATION CHEMICALCHEMICAL - - Benzene, smoking, paint, Benzene, smoking, paint,

petroleum, pesticides.petroleum, pesticides. DRUGSDRUGS - - Alkylating agents, Topo Alkylating agents, Topo

isomerase II inhibitors, isomerase II inhibitors, Chloramphenicol and phenyl butazoneChloramphenicol and phenyl butazone. .

CLINICAL FEATURESCLINICAL FEATURES Age of onset - AdultAge of onset - Adultonset and incidence onset and incidence

increases increases with agewith age M/F M/F - 4.4 : 3- 4.4 : 3 FatigueFatigue LOW/ LOALOW/ LOA Fever with or without infectionFever with or without infection Bleeding symtomsBleeding symtoms Bone painBone pain LymphadenapathyLymphadenapathy HepatosplenomegalyHepatosplenomegaly GI, PUL, Intra cranial, Retinal hhage (APL – GI, PUL, Intra cranial, Retinal hhage (APL –

M3)M3) Chloroma ( M1 M2)Chloroma ( M1 M2) Gum hypertrophy (M4 M5 )Gum hypertrophy (M4 M5 )

Anemia with dec Retic count

WBC – mean 15,000 <5000 in 25 – 40% > 100,000 in 20% No malig cells in 5% Dysfunction +

Platlets - < 100,000 in 75%< 25000 in 25%Dysfunction +

BLOOD PARAMETERS

CLASSIFICATIONCLASSIFICATIONSS

FABFAB Based on Morphological charecteristicsBased on Morphological charecteristics BLAST cells > 30 %BLAST cells > 30 %

WHOWHO BLAST cells > 20 %BLAST cells > 20 % Based on Morphology, Molecular and CF.Based on Morphology, Molecular and CF.

FABFAB M0M0 - Minimal diff- Minimal diff M1M1 - Myeloblastic without maturation- Myeloblastic without maturation M2M2 - Myeloblastic with maturation- Myeloblastic with maturation M3M3 - Promyelocytic- Promyelocytic M4M4 - Myelomonocytic- Myelomonocytic M4E0M4E0 - Marrow eosinophilia- Marrow eosinophilia M5M5 - Monocytic- Monocytic M6M6 - Erythroleukemia- Erythroleukemia M7M7 - Megakaryoblastic- Megakaryoblastic

WHOWHO AML IAML I – – GENETIC GENETIC abnormalitiesabnormalities

t ( 8/21), inv (16), t (16/16)t ( 8/21), inv (16), t (16/16) MLL abnormalitiesMLL abnormalities APL t ( 15/ 17)APL t ( 15/ 17)

AML II-AML II- Following Following myelodysplasiamyelodysplasia/ / myeloproliferative disordersmyeloproliferative disorders

AML III-AML III- Following Following DRUGDRUG induced induced myelodysplasiamyelodysplasia

AML IVAML IV – M0 to M7 of FAB , panmyelosis, – M0 to M7 of FAB , panmyelosis, basophilic and myeloid sarcomabasophilic and myeloid sarcoma

PROGNOSISPROGNOSIS GOODGOOD

Young ageYoung age Chromosomal defects Chromosomal defects

(t8/21, inv 16, (t8/21, inv 16, t15/17)t15/17)

Rapid induction of CRRapid induction of CR Long duration of CRLong duration of CR

POORPOOR Advanced age ( > 60)Advanced age ( > 60) Chrom defects ( inv Chrom defects ( inv

3, -7 )3, -7 ) Asso med illnessAsso med illness Prolonged Prolonged

cytopeniascytopenias Prev myelodysplasiaPrev myelodysplasia Drug induced AMLDrug induced AML Delayed and short Delayed and short

duration of CRduration of CR

MANAGEMENMANAGEMENTT

REMISSION INDUCTIONREMISSION INDUCTION

POST REMISSION MANAGEMENTPOST REMISSION MANAGEMENT

REMISSION INDUCTIONREMISSION INDUCTION(7&3 REGIME)(7&3 REGIME)

CYTARABINECYTARABINE 100 – 200 mg / sq m/ day IV infusion 7 100 – 200 mg / sq m/ day IV infusion 7

daysdays

ANTHRACYCLINEANTHRACYCLINE Daunorubicin – 45- 60mg/sq m/day IV 3 Daunorubicin – 45- 60mg/sq m/day IV 3

days days IdarubicinIdarubicin - 12 mg/sq m/ day IV - 12 mg/sq m/ day IV

With or without With or without ETOPOSIDEETOPOSIDE

COMPLETE COMPLETE REMISSIONREMISSION

BloodBlood WBC >1500WBC >1500 Platlet > 1 LacPlatlet > 1 Lac RBC count not consideredRBC count not considered No BLAST cellsNo BLAST cells

BMBM Trilineage cellularity > 20%Trilineage cellularity > 20% Blast cellBlast cell < 5% < 5% NO Auer rodsNO Auer rods RT PCR/ FISH to r/o residual leukemic RT PCR/ FISH to r/o residual leukemic

cellscells

If 7 & 3 RegimeIf 7 & 3 Regime 50% - CR50% - CR

start 5 & 2 Regimestart 5 & 2 Regime 25% - CR25% - CR 25% - NO CR25% - NO CR

NO CRNO CR 50% - Drug Resistance50% - Drug Resistance 50% - Fatal complications of Drugs50% - Fatal complications of Drugs

POST REMISSION POST REMISSION MANAGEMENTMANAGEMENT

HIGH DOSE HIGH DOSE CYTARABINECYTARABINE 3-4 cycles3-4 cycles 3 g/sq m / day bd 3 g/sq m / day bd

on 1,3 & 5 th dayon 1,3 & 5 th day

STEM CELL TxSTEM CELL Tx AutologousAutologous allogenicallogenic

LESS INTENSIVE LESS INTENSIVE CHEMOTHERAPYCHEMOTHERAPY

STEM CELL TxSTEM CELL Tx Non myeloablative Non myeloablative

AllogenicAllogenic

AGE < 65 yrs AGE > 65 YRS

TREATMENT OF APL TREATMENT OF APL ( M3)( M3)

TRETINOINTRETINOIN( Maturation of blast cells,No ( Maturation of blast cells,No DIC)DIC) 45 mg/ sqm/day Untill 45 mg/ sqm/day Untill

remissionremission ANTHRACYCLINESANTHRACYCLINES

Maintanance therapyMaintanance therapy Tretnoin or chemotherapyTretnoin or chemotherapy

RELAPSERELAPSE

STEM CELL TX