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A CASE OF ACUTE MYELOID LEUKEMIA. PROF S SHIVAKUMAR P SENTHIL KUMAR MD PG. Rajendran 42 yrs/ M c/o Multiple swellings in the neck and submandibular region Fever Breathlessness 3months Pain abdomen Loss of appetite/ Loss of wt.
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A CASE OF ACUTE MYELOID LEUKEMIA PROF S SHIVAKUMAR P SENTHIL KUMAR MD PG
Rajendran • 42 yrs/ M • c/o • Multiple swellings in the neck and submandibular region • Fever • Breathlessness 3months • Pain abdomen • Loss of appetite/ Loss of wt. • No cough with sputum • No dysuria, rashes, jaundice • Bowel and bladder - N
Past H/o • No DM/ HTN/ IHD/ PT/ BA/ STROKE • Personal H/o • Smoker/ alcoholic • Agricultural worker • Family H/o • Nil • Treatment H/o • Pt on ATT for PL effusion past 3 months
O/E • Conscious • Oriented • Febrile • Pallor + • Clubbing+ • Subconjunctival hemorrhage • Submandibular/ cervical / supraclavicular LN + • No icterus/ cyanosis/ PE/ JVP.
RS • BS Lt mamary/ infra axillary/ infrascapular areas • Stony dullness • Chest wall movements Lt side • CVS • S1 S2 + • No murmur • ABD • No organomegaly • No FF
LAB • Hemogram • Hb - 5.6 g/dl • TLC - 30,100/cu mm • DC - blast 60% P24 L 04 Myelocyte 12 • Platlets - 20.000/ cu mm • RBC - 1.6 million/ cu mm • PCV - 15 %
PERIPHERAL SMEAR • RBC - Normochromic Normocytes and few hypochromic microcytes. - No hemoparasites seen • WBC - Count increased with BLASTS showing occasional Auer Rods. • PLATLETS- Diminished
BONE MARROW • Hypercellular Marrow replaced by Leukemic cells with BLAST showing MYELOID MONOCYTIC differentiation up to 70 % • ERYTHROPOIESIS • MEGAKARYOPOIESIS • CYTOCHEMISTRY • MPO - Inconclusive • PAS - Neg
RFT • Urea - 32 mg/dl • Creatinine - 0.8 mg/dl • Bl sugar - 105 mg/dl • LFT • TB - 0.7 mg/dl • DB - 0.3 mg/ dl • SGOT - 24 Iu/L • SGPT - 22 Iu/L • SAP - 1O5 Iu/L
CXR - Lt pleural effusion • ECG - WNL • USG ABD - Lt pleural effusion - LIVER/ SPLEEN normal • SPUTUM • AFB - Neg • Grams stain - Neg • Malig cells - Neg
Pleural Fluid • Protein - 4.6 g/dl • Sugar - 84 mg/dl • WBC - 2600/ cu mm ( P 11 L 39 ) • RBC - 30,000/cu mm • Smear - +ve for MALIGNANT CELLS • Grams stain - No organisms • AFB - Neg
Problems • Fever • Lymphadenopathy • Pleural effusion • Subconjunctival hemorrhage • Loss of wt
DIAGNOSIS ACUTE MYELOID LEUKEMIA – M4 WITH MALIGNANT PLEURAL EFFUSION
ETIIOLOGY • HEREDITY - Downs , Klinefelters, patau, Chromosomal breakage syndromes • RADIATION • CHEMICAL - Benzene, smoking, paint, petroleum, pesticides. • DRUGS - Alkylating agents, Topo isomerase II inhibitors, Chloramphenicol and phenyl butazone.
CLINICAL FEATURES • Age of onset - Adult onset and incidence increases with age • M/F - 4.4 : 3 • Fatigue • LOW/ LOA • Fever with or without infection • Bleeding symtoms • Bone pain • Lymphadenapathy • Hepatosplenomegaly • GI, PUL, Intra cranial, Retinal hhage (APL – M3) • Chloroma ( M1 M2) • Gum hypertrophy (M4 M5 )
BLOOD PARAMETERS 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 +
CLASSIFICATIONS • FAB • Based on Morphological charecteristics • BLAST cells > 30 % • WHO • BLAST cells > 20 % • Based on Morphology, Molecular and CF.
FAB • M0 - Minimal diff • M1 - Myeloblastic without maturation • M2 - Myeloblastic with maturation • M3 - Promyelocytic • M4 - Myelomonocytic • M4E0 - Marrow eosinophilia • M5 - Monocytic • M6 - Erythroleukemia • M7 - Megakaryoblastic
WHO • AML I – GENETIC abnormalities • t ( 8/21), inv (16), t (16/16) • MLL abnormalities • APL t ( 15/ 17) • AML II- Following myelodysplasia/ myeloproliferative disorders • AML III- Following DRUG induced myelodysplasia • AML IV – M0 to M7 of FAB , panmyelosis, basophilic and myeloid sarcoma
GOOD Young age Chromosomal defects (t8/21, inv 16, t15/17) Rapid induction of CR Long duration of CR POOR Advanced age ( > 60) Chrom defects ( inv 3, -7 ) Asso med illness Prolonged cytopenias Prev myelodysplasia Drug induced AML Delayed and short duration of CR PROGNOSIS
MANAGEMENT • REMISSION INDUCTION • POST REMISSION MANAGEMENT
REMISSION INDUCTION (7&3 REGIME) • CYTARABINE • 100 – 200 mg / sq m/ day IV infusion 7 days • ANTHRACYCLINE • Daunorubicin – 45- 60mg/sq m/day IV 3 days • Idarubicin - 12 mg/sq m/ day IV • With or without ETOPOSIDE
COMPLETE REMISSION • Blood • WBC >1500 • Platlet > 1 Lac • RBC count not considered • No BLAST cells • BM • Trilineage cellularity > 20% • Blast cell < 5% • NO Auer rods • RT PCR/ FISH to r/o residual leukemic cells
If 7 & 3 Regime • 50% - CR • start 5 & 2 Regime • 25% - CR • 25% - NO CR • NO CR • 50% - Drug Resistance • 50% - Fatal complications of Drugs
HIGH DOSE CYTARABINE 3-4 cycles 3 g/sq m / day bd on 1,3 & 5 th day STEM CELL Tx Autologous allogenic LESS INTENSIVE CHEMOTHERAPY STEM CELL Tx Non myeloablative Allogenic POST REMISSION MANAGEMENT AGE < 65 yrs AGE > 65 YRS
TREATMENT OF APL ( M3) • TRETINOIN( Maturation of blast cells,No DIC) • 45 mg/ sqm/day Untill remission • ANTHRACYCLINES • Maintanance therapy • Tretnoin or chemotherapy
RELAPSE STEM CELL TX