General

AML ALL Rapid onset & Rapid progression High Mortality Plenty of Blasts >20% (in PS or BM) low RBC, low WBC, low PLT, leukemic infiltration Young adults Palor, fatigue, weakness, anaemia Bleeding, bruising, petechial hemorrhages Infections, pneumonia, meningitis Hepatosplenomegaly Children Growth failure, fever, anaemia Bleeding Lymphadenopathy Hepatosplenomegaly

CML CLL Indolent course. More mature forms are seen in the PS like lymphocyte and neutrophils Blasts in PS or BM is less than 20% (5-10%) WBC counts are very high Older adults Fever, anaemia Bleeding Hepatosplenomegaly Weight loss 3 phases: Chronic, Accelerated, Blast crisis Insidious onset Philadelphia chromosome, t(9:22) Leucocytosis Old age May be asymptomatic. Lymphadenopathy No need aggressive therapy

Age Clinical feature

Diagnosis

High clinical suspicion Family history, past history Simple PS examination. Other lab tests: Serum uric acid, LDH, RFT, Sr.Ca, electrolytes

PS examination RBC normocytic normochromic WBC count increased, rarely decreased or normal. Majority of cells are Immature cells- Blasts PS shows > 20% Myeloblasts Mature neutrophils are less Morphology of AML M0- M7 type Low platelets Bone marrow examination Hypercellular Marrow Blasts are > 20% Blasts with intracytoplasmic rodsAuer Rods Increased M: E ratio Less of Megakaryocytes Cytochemistry Myeloblasts are +ve for Sudan black B & Myeloperoxidase (MPO) Lymphoblasts are +ve for Periodic acid schiff (PAS) AML M4 & M5 blasts are +ve for Non- specific esterase (NSE) Immunophenotyping Identify cells by surface markers using antibodies Cytogenetics t(8;21) in AML M2 t(15;17) in AML M3 inv16 in AML M4

High clinical suspicion PS & BM study (morphological diagnosis) Morphology of ALL L1, L2, L3 Lymph node aspiration & biopsy Immunophenotyping Cytogenetics Imaging (USG scan, CT) Neoplastic cells are CD10 +ve & most are Pre B cell type. 2% of child ALL & 20-30% of adult onset ALL has t(9;22)

Clonal B cells are seen with arrest in maturation (arrested in between Pre-B cell & Mature B cell) All neoplastic cells show surface CD 5 +ve Mature lymphocyte markers like CD 19, 20, 21 PS examination o Total count increased, majority are mature lymphocytes, smudge cells, (smear cells, basket cells), less of neutrophils Some prolymphocytes + Identical tumor of lymph node SLL (small lymphocytic lymphoma) Autoimmune HA, Autoimmune Thrombocytopenia is common (10% of cases) May progress to aggressive types o Prolymphocytic leukemia o Diffuse large B cell lymphoma (Richter syndrome)

Morphology of AML (M0-M7 types) M0 M1 M2 M3 Undifferentiated Without maturation With maturation Promyelocytic Numerous cytoplasmic granules- promyelocytes Auer rods are plenty Complication of DIC seen in most cases Classical t(15;17) Treated with ATRA (all trans retinoic acid) Myelomonocytic Acute monocytic leukemia Commonly present with gingival swellings & skin nodules Acute Erythroleukemia Di Guglielmo disease Binucleated & megaloblastic erythroid precursors are in excess Megakaryocytic

Staging of CLL Modified Rai staging (USA) o Low risk Lymphocytosis in the blood and marrow only o Intermediate risk Lymphocytosis with Lymphadenopathy / splenomegaly or hepatomegaly o High risk Lymphocytosis with Anemia or thrombocytopenia Binet staging (Europe) o Stage A Hb >/=10 g/dL, Platelets >/= 100 X 109/L, and fewer than 3 lymph node areas involved. o Stage B Hb and Platelet levels as in stage A and 3 or more lymph node areas involved. o Stage C Hb < 10 g/dL or Platelets < 100 X 109/L, or both

M4 M5

M6

M7

Differences between CML & Leukemoid Reaction CML Malignancy Hepatosplenomegaly Large spleen Slow course Total count Increased Thrombocytosis LAP decreased Ph chromosome Basophilia Leukemoid reaction Inflammatory lesion Hepatomegaly Mild spleen if present Short duration Increased but not much Platelets- Normal LAP increased No Ph chromosome Antibiotics Myeloproliferative disorder 1. Chronic myeloid leukemia (CML) 2. Polycythaemia vera 3. Essential thrombocytosis 4. Myelofibrosis.

Marrow fibrosis (cytopenias) Acute leukemia

Peripheral B cell neoplasm These are Chronic Lymphocytic Leukemia (CLL) & Small Lymphocytic Lymphoma (SLL) Identical in morphology, genoptype & phenotype Degree of PS lymphocytosis is different (higher in CLL) CLL Blood phase of neoplasm SLL Tissue phase of neoplasm Both can co exist in same patient