Download - A CASE OF ACUTE MYELOID LEUKEMIA PROF S SHIVAKUMAR P SENTHIL KUMAR MD PG P SENTHIL KUMAR MD PG
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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
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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
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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
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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.
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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
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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 %
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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
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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
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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
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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
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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
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Problems Problems
FeverFever LymphadenopathyLymphadenopathy Pleural effusionPleural effusion Subconjunctival hemorrhageSubconjunctival hemorrhage Loss of wtLoss of wt
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DIAGNOSISDIAGNOSIS
ACUTE MYELOID LEUKEMIA ACUTE MYELOID LEUKEMIA – M4 WITH MALIGNANT – M4 WITH MALIGNANT PLEURAL EFFUSION PLEURAL EFFUSION
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ACUTE ACUTE MYELOID MYELOID LEUKEMIALEUKEMIA
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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. .
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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 )
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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
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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.
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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
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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
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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
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MANAGEMENMANAGEMENTT
REMISSION INDUCTIONREMISSION INDUCTION
POST REMISSION MANAGEMENTPOST REMISSION MANAGEMENT
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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
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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
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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
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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
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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
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RELAPSERELAPSE
STEM CELL TX
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