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ACUTE LEUKAEMIA

ACUTE LEUKAEMIA. LEUKAEMIA. A disorder characterised by the accumulation of malignant white cells in the bone marrow and peripheral blood. 2 main types: Acute leukaemia Chronic leukaemia. ACUTE LEUKAEMIA. A malignant disorder in which blasts constitute >30% of the bone marrow cells

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ACUTE LEUKAEMIA

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  1. ACUTE LEUKAEMIA

  2. LEUKAEMIA • A disorder characterised by the accumulation of malignant white cells in the bone marrow and peripheral blood. 2 main types: • Acute leukaemia • Chronic leukaemia

  3. ACUTE LEUKAEMIA A malignant disorder in which blasts constitute >30% of the bone marrow cells 2 main groups: • Acute Myeloid Leukaemia (AML) • Acute Lymphoblastic Leukaemia (ALL)

  4. Normal White Cell Development

  5. Epidemiology and Aetiology • ALL commoner in childhood with a peak age of 4 years • AML commoner in adults • No proven geographical or environmental agents

  6. Aetiology • Genetic / Constitutional • Down’s syndrome • Fanconi’s anaemia • Acquired • Myelodysplasia • Chemotherapy/radiotherapy • Chronic myeloproliferative disorders

  7. FAB CLASSIFICATION M1 myeloblastic undifferentiated M2 myeloblastic with differentiaion M3 promyelocytic M4 myelomonocytic M5 monoblastic M6 erythroleukaemia M7 megakaryoblastic WHO CLASSIFICATION AML with recurrent genetic abnormalities AML with multilineage dysplasia AML therapy related AML not otherwise categorised AML of ambiguous lineage ACUTE MYELOID LEUKAEMIA CLASSIFICATION

  8. ACUTE LEUKAEMIAS Basis of disease: maturation defect of BM stem cells Cell proliferation might be s lo w e r than normal!!! abnormal blasts dominate the BM picture normal haemopoietic elements are blocked – this is due not only to space occupation lymphoid leukaemias belong to lymphoma/ leukaemia group

  9. CLINICAL APPEARANCE OF ACUTE LEUKAEMIAS Weakness - anaemia Fever, infection - granulocytopenia Hemorrhage - thrombocytopenia - (anywhere in the body) Bone pain, tenderness - subperiosteal leukaemic infiltration Meningeal symptoms - CNS involvement / (headache, nausea, vomit, subarachnoidal bleeding cerebral palsy, intracerebral, meningeal infiltration)

  10. Symptoms, specific to certain leukaemias AML M3 - (promyelocytic) DIC AML M1-2 - soft tissue,or subperiostal infiltration AML 4-5 - skin, gum infiltration

  11. Clinical Features • Bone marrow failure • Anaemia, bruising/bleeding, DIC (M3), infection • Lymphadenopathy / hepatosplenomegaly • Commoner in ALL • Tissue infiltration • CNS, testes (ALL), gum hypertrophy (M4) • Increased cellular catabolism

  12. ACUTE LEUKAEMIA - PURPURA

  13. ACUTE LEUKAEMIA - HAEMORRHAGE

  14. ACUTE LEUKAEMIA – HERPES ZOSTER

  15. ACUTE MYELOID LEUKAEMIA – GUM HYPERTROPHY

  16. ACUTE MYELOID LEUKAEMIA – SKIN INFILTRATION

  17. Laboratory Features Blood Count • Anaemia, Thrombocytopenia, Neutropenia • High or low white cell count (WCC) • Circulating blasts Coagulation • Often abnormal • Disseminated Intravascular Coagulation(DIC)

  18. Laboratory Features Bone Marrow (BM) Aspirate • Marrow is usually replaced by blasts with little or no remaining normal haemopoietic tissue Trephine Biopsy • Useful if the marrow is hypocellular or fibrotic

  19. NORMAL BONE MARROW

  20. ACUTE MYELOID LEUKAEMIA

  21. ACUTE LYMPHOBLASTIC LEUKAEMIA

  22. Laboratory Features Diagnosis • Morphology • Cytochemistry • Immunophenotyping • Cytogentics

  23. Morphology • Bone marrow and peripheral blood • BM shows >30% blasts • Cells often contain granules or inclusions called Auer rods

  24. ACUTE MYELOID LEUKAEMIA – AUER ROD

  25. Cytochemistry AML • Sudan black, Myeloperoxidase, Chloroacetate Esterase • Monoblastic – Non Specific Esterase ALL • B lineage – PAS • T lineage – Acid Phosphatase

  26. ACUTE LYMPHOBLASTIC LEUKAEMIA - PAS

  27. Immunophenotyping • Use of antibodies to identify cell antigens (clusters of differentiation or CD) • The pattern of antigens expressed by the cells correlates with lineage and maturity • Eg AML - CD 13, CD33 positive, CD19, CD20 negative

  28. Cytogenetics • Chromosomal abnormalities are found in the blasts in 70% of cases of AML and 90% of ALL • Important in the pathogenesis of the disease • Important for diagnosis • Prognostic implications • Eg t(15;17) and M3 AML

  29. ACUTE MYELOID LEUKAEMIA – PROMYELOCYTIC (M3)

  30. LABORATORY FINDINGS Anaemia variable severity WBC 50 % < 10000/mm3 20 % > 100000/mm3 Blasts both in peripheral and BM smears, HIATUS LEUKAEMICUS Thrombocyte < 100000 / mm3 Rarely : aleukaemic leukaemia Peripheral pancytopaenia : BM biopsy- RULE OUT - aplastic anaemia

  31. LABORATORY FINDINGS CYTOCHEMISTRY ALL AML PAS + - Tdt + (95 % ) - (95 %) myeloperoxidase + (M1-3) NON spec. esterase - + (M4-5)

  32. Clinical Management • Supportive care • Remission induction • Maintenance therapy • Bone marrow transplantation • Treatment of relapse

  33. Clinical Management AML • Remission induction + consolidation usually with 4 courses of chemotherapy • M3 – chemotherapy + ATRA • Bone Marrow or stem cell transplantation for those with poor prognosis disease who have a suitable donor

  34. Clinical Management • ALL • Remission induction + consolidation • CNS prophylaxis • Maintenance therapy for 2-3 years • Bone marrow or stem cell transplant for those with poor prognosis disease with a suitable donor

  35. Prognosis Childhood ALL • 70% cure • Poor prognosis • High WCC • Male • Age <1yr or>15yr • Poor cytogenetics

  36. Prognosis • AML and adult ALL • 30% cure • Poor prognosis • Age > 60 yr • Poor cytogenetics • Failure to achieve remission after 1st course of chemotherapy • Secondary AML

  37. PROGNOSIS , THERAPY ALL - 2-10 5 year survival over 60 % CHEMOTHERAPY T cell, and adult form- grave AML - BM TRANSPLANTATION

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