1 / 31

Acute leukaemias

Acute leukaemias. Dr. Farhana Zakaria. 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.

Gabriel
Download Presentation

Acute leukaemias

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

  27. THANK YOU

More Related