acute leukaemias n.
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Acute leukaemias

Acute leukaemias

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Acute leukaemias

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  1. Acute leukaemias Dr. Farhana Zakaria

  2. Acute leukaemias are malignant clonal disorders originating in haematopoetic stem cells characterised by the proliferation of poorly- differentiated blast (immature) cells in the bone marrow and a rapidly progressive fatal course if untreated. • There is an arrest in the differentiation of immature cells into functionally mature cells.

  3. There are 2 main groups of acute leukaemias : • Acute lymphoblastic leukaemia • Acute myeloblastic leukaemia

  4. Predisposing factors • Ionizing radiation • Drugs • Chemicals • Genetic disorders • Acquired disorders – PNH and AA and • MDS

  5. Classification of acute leukaemias FAB classification for ALL: • ALL-L1: small, homogenous cells with inconspicuous / 1-2 nucleoli. • ALL-L2: large cells with variable size with 1-2 nucleoli. • ALL-L3: large cells, homogenous , finely stippled chromatin with basophilic vacuolated cytoplasm.

  6. WHO classification of ALL

  7. Diagnosis of acute leukaemias • >20% blasts in the bone marrow • Morphology • Cytochemistry • Immunophenotyping • Cytogenetics • Molecular genetics

  8. Morphology Blast cells are large cells with : • High N:C ratio • Nucleus is large with open chromatin • Nucleoli- 1- 5 • Thin rim to moderate amount of cytoplasm

  9. Cytochemistry in acute leukaemias • Are used to identify certain enzymes or other substances in the cytoplasm of hematopoetic cells. Various stains used are: • Myeloperoxidase (MPO) • Sudan black B (SBB) • Non specific esterase (NSE) • Periodic acid schiff stain (PAS)

  10. Cytochemistry in AML and ALL

  11. Immunophenotyping • Leukaemic cells of different types express cell surface and cytoplasmic antigens which can be characterised using monoclonal antibodies directed against those antigens. • There are 2 techniques in immunophenotyping: • Immunocytochemistry • Flow cytometry

  12. Immunophenotyping in ALL

  13. Immunophenotyping is useful in:1.Characterising ALL/AML using lymphoid and myeloid MCAs2.Distinguishing B or T cell lineage3.Diagnosing M0, M1, M6 and M7 in particular4.Assessing prognosis in ALL on the basis of ontogeny of lymphoblasts

  14. Cytogenetics • Leukaemic blasts arise from the abnormal clone having an acquired chromosomal abnormality. • Classification of acute leukaemias has incorporated some of these in the classification.M2 t(8;21)(q22;q22)M3 and M3V t(15;17)(q22;21)M4 E0 inv(16)(p13q22)M5 t(9;11) (p21-22;q23)L1ALL high hyperdiploidyL1 or L2 ALL t(12;21) (p12;q22)L1 or L2 t(9;22) (q34;q11) common ALL/BCR-ABL fusion

  15. Molecular Genetics • Molecular genetics is based on DNA analysis by • Southern blot technique • PCR • RTPCR- for analysis of RNA by reverse transcriptase

  16. ACUTE LYMPHOBLASTIC LEUKAEMIA • Malignant neoplasm of haematopoetic stem cells of lymphoid lineage arising in the bone marrow. • Clinical features: • Age and sex: Majority of the cases are aged 1-5yrs and these carry a better prognosis than children <1yr or >10yr. • Second peak is observed in adults in the age of 30-40yrs. • Slight male preponderance.

  17. Symptoms • Most of the symptoms are because of anaemia, infections are due to neutropenia and bleeding tendency due to thrombocytopenia. • Fatigue and pallor. • Infections: Respiratory infections are common in cases where neutrophils are decreased. • Haemorrhages: Purpuric rash or ecchymosis. Gum bleeding, epistaxis and fundal haemorrhages are not uncommon. • Bone pains

  18. Lymphadenopathy • Hepatosplenomegaly • Mediastinal mass • CNS involvement: Head ache and vomiting.

  19. Haematologic Findings • The hallmark is the presence of blasts in blood and bone marrow with reduction of normal haemopoietic cells. • Increase in white cell count: White cell count is markedly elevated varying from 20x109/L to 200x109/L. • Differential count and blast cells: peripheral smear reveals usually 40-95% blast cells. • Cytochemistry of blast cells: Lymphoblasts are MPO/ Sudan black B negative. PAS demonstrates block positivity. • Anaemia • Neutropenia • Decreased platelet count

  20. FAB subtypes of ALL

  21. FAB subtypes of ALL

  22. Bone marrow examination: • Cellularity: Bone marrow is markedly hypercellular and normal fat and haemopoietic cells are replaced by proliferating blast cells. • Blast cells: Blasts cells constitute 30-100% of the marrow cells. • Haemopoiesis: There is reduction of erythroid and myeloid precursors. Megakaryocytes gradually decrease and at a later stage, no megakaryocytes may be discerned in bone marrow.

  23. Morphology of blast cells: Morphology of the blast cells in bone marrow is more consistent than in peripheral blood. • Marrow aspiration is especially useful in diagnosing ALL in subleukaemic/ aleukaemic cases. • Other investigations which can be carried out on bone marrow aspirate are:CytochemistryCytogeneticsImmunophenotyping

  24. Biochemical investigations: • Increased serum uric acid: • Increased serum phosphate • Decreased serum calcium • Increased LDH

  25. Differential Diagnosis: • Non Hodgkins lymphoma with spill over of lymphoma cells in peripheral blood • Infectious mononucleosis

  26. ALL Prognostic factors