Acute Leukaemia (AML/ALL) & WBC Disorders: OmpathStudy

COMPREHENSIVE REVISION NOTES BATCH 2 Topics 7 – 14 --- TOPIC 7: WHITE BLOOD CELLS — FUNCTION & DISORDERS Definition: Leucocytes — nucleated blood cells of the immune system Leukos (Greek) = white kytos = cell Classification by Function: (★) Cell % of WBC Primary Role --- --- --- Neutrophils 60–70% Bacterial/fungal phagocytosis — first responders Eosinophils 1–4% Parasitic infections (★), allergic/IgE reactions Basophils <1% Allergic reactions, release histamine and heparin Monocytes 2–8% Phagocytosis; differentiate into tissue macrophages Lymphocytes 20–40% Adaptive immunity (T-cells, B-cells, NK cells) Eosinophils release major basic protein (MBP) and eosinophil cationic protein, recruited by IL-5 , to kill helminths and parasites (★) Key Terminology: (★) Term Meaning --- --- Leucocytosis ↑ WBC count Leucopenia ↓ WBC count Neutrophilia ↑ neutrophils (bacterial infection, stress) Neutropenia ↓ neutrophils, ANC <1.5 × 10⁹/L Lymphocytosis ↑ lymphocytes (viral infection, CLL) Lymphopenia ↓ lymphocytes (HIV, steroids) Eosinophilia ↑ eosinophils (parasites, allergy, drugs) Erythrocytosis ↑ RBCs Thrombocytopenia ↓ platelets Thrombocytosis ↑ platelets Neutropenia: Mild: 1.0–1.5 ×10⁹/L Moderate: 0.5–1.0 ×10⁹/L Severe: <0.5 ×10⁹/L — high infection risk (★) Most common cause in clinical practice: chemotherapy (★) Other causes: aplastic anaemia, viral infections, drugs (clozapine, carbimazole), autoimmune, severe sepsis Management: G-CSF, isolate from infection sources, prompt antibiotics if febrile (febrile neutropenia = medical emergency) --- TOPIC 8: ACUTE LEUKAEMIA (AML & ALL) Etymology: Leukos = white haima = blood Definition: Malignant clonal proliferation of immature haematopoietic blasts WHO criterion: ≥20% blasts in bone marrow or peripheral blood confirms acute leukaemia (★) Acute vs Chronic: Acute: blasts dominate, rapid onset, pancytopenia + circulating blasts Chronic: mature cells dominate, indolent course --- ACUTE MYELOID LEUKAEMIA (AML) Definition: Clonal proliferation of myeloid blasts (myeloblasts, monoblasts, etc.) Clinical Presentation: (★) Anaemia → fatigue, pallor Neutropenia (despite high WCC — non-functional blasts) → fever, infections Thrombocytopenia → bruising, bleeding, petechiae Gum hypertrophy, skin infiltration (especially monocytic subtypes) Diagnosis: (★) Gold standard: bone marrow aspirate + trephine biopsy with cytogenetics and immunophenotyping Auer rods — pathognomonic pink needle-like cytoplasmic inclusions in myeloblasts (★) Flow cytometry for immunophenotyping Peripheral smear alone is insufficient for definitive diagnosis Cytochemical Stains — Confirming Lineage: (★) Stain Lineage --- --- Myeloperoxidase (MPO) Myeloid — most specific (★) Sudan Black B Myeloid (less specific than MPO) Non-specific esterase (NSE) Monocytic (M4/M5 subtypes) Periodic acid-Schiff (PAS) Lymphoid (ALL) and erythroid TdT (Terminal deoxynucleotidyl transferase) Lymphoblasts — confirms ALL (★) TRAP Hairy cell leukaemia FAB Classification of AML: (★) Subtype Name Key Feature --- --- --- M0 Undifferentiated — M1 Without maturation — M2 With maturation t(8;21) M3 Acute promyelocytic leukaemia (APL) t(15;17) — PML-RARA fusion; DIC risk ; treated with ATRA (★) M4 Myelomonocytic inv(16) M5 Monocytic Gingival hypertrophy and skin infiltration (★) M6 Erythroleukaemia — M7 Megakaryoblastic — --- ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) Definition: Clonal proliferation of lymphoid blasts (B- or T-lineage); most common childhood leukaemia Diagnosis: TdT positive — confirms lymphoblast origin (★) PAS positive Cytogenetics/molecular: best sample = bone marrow aspirate (preferred over peripheral blood for cytogenetic/molecular analysis) (★) Immunophenotyping markers: (★) Marker Lineage --- --- CD19, CD10, CD20 B-cell ALL CD3 T-cell ALL (★) CD33, CD13 Myeloid (AML) --- TOPIC 9: CHRONIC LEUKAEMIAS CHRONIC MYELOID LEUKAEMIA (CML) Definition: Clonal myeloproliferative disorder of granulocyte precursors Pathognomonic finding: (★) t(9;22)(q34;q11) — the Philadelphia chromosome Forms BCR-ABL fusion gene → constitutive tyrosine kinase activity → uncontrolled proliferation Clinical Presentation: (★) Fatigue, weight loss, splenomegaly (massive) Very high WCC (often 100 ×10⁹/L) Neutrophilia with left shift and basophilia — classic triad (★) Investigations to confirm diagnosis: (★) FBC + PBF: leucocytosis with full spectrum of granulocyte maturation, basophilia Bone marrow aspirate + trephine biopsy with cytogenetic analysis Quantitative RT-PCR for BCR-ABL transcripts — used for diagnosis confirmation AND monitoring treatment response (★) FISH — detects Philadelphia chromosome in interphase cells (doesn't require dividing cells, faster than conventional cytogenetics) (★) Conventional cytogenetics (karyotyping) — detects t(9;22) directly but requires metaphase cells Treatment: Tyrosine kinase inhibitors (TKIs) : imatinib (first-line), dasatinib, nilotinib — target BCR-ABL (★) Distinguishing CML from Polycythaemia Vera: (★) CML: BCR-ABL