ALL

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ALL

  1. 1. Acute leukemia- Dr Dinesh Bhurani, DM, FRCPA Senior bone marrow transplant physician Rajiv Gandhi Cancer Inst & RC, Delhi
  2. 2. ALL CLL Lymphomas MM naïve B-lymphocytes Plasma Lymphoid cells progenitor T-lymphocytes AML Myeloproliferative disordersHematopoietic Myeloid Neutrophilsstem cell progenitor Eosinophils Basophils Monocytes Platelets Red cells
  3. 3. Incidence
  4. 4. Acute myeloid leukaemia
  5. 5. ALL
  6. 6. Cytopenia
  7. 7. Production failure• Stem cell defect – Apastic anaemia• Bone marrow suppression – Drugs – Infections eg malaria, dengue, HIV• Ineffective haemopoiesis – Megaloblastic anaemia – Myelodysplastic syndrome
  8. 8. Production failure• Bone marrow infiltration – Haematological malignancy – Non haematological malignancy• Marrow fibrosis – Primary – Secondary• Haemophagocytic syndrome
  9. 9. Increased consumption• Hypersplenism• Immune cytopenia
  10. 10. Peripheral smear• Oval macrocytes, hypersegmented neutrophils – megaloblastic anaemia• Leuko-erythroblastic blood picture – marrow infiltration• Leuko-erythroblastic picture with tear drop cells – marrow fibrosis• Blast or atypical lymphoid cells – haematological malignancy• Dysplastic feature – MDS, drugs or HIV infection
  11. 11. Leukaemia• Pancytopenia or bicytopenia – Can it be haematological malignancy? CBC & peripheral smear• Avoid steroids prior to confirmation of diagnosis
  12. 12. Bone marrow aspirate andbiopsy both are essential.
  13. 13. Acute Leukaemia• Comprises approximately 30 percent of all childhood malignancies• An incidence of 2.8 cases per 100,000• The peak incidence 2-5 Yrs• Studies of the relationship between childhood ALL, urban/rural status and population density, as well as other possible etiologic factors (eg, environmental exposures, abnormal immune response to common infections) have yielded inconsistent results
  14. 14. Acute leukaemia• Persistent or progressive lymphadenopathy that does not respond to antibiotic therapy suggests the need for more extensive evaluation.
  15. 15. Differential diagnosis• Juvenile idiopathic arthritis• Osteomyelitis• Epstein-Barr virus• Idiopathic thrombocytopenic purpura• Pertussis, parapertussis• Aplastic anemia• Acute infectious lymphocytosis• Other malignancies with bone marrow involvement (eg, neuroblastoma, retinoblastoma, rhabdomyosarcoma, and Ewing sarcoma
  16. 16. Acute lymphoblastic leukaemia
  17. 17. Etiology
  18. 18. Leukaemogenesis
  19. 19. Leukaemogenesis
  20. 20. Classification
  21. 21. Acute myeloid leukaemia
  22. 22. Diagnosis
  23. 23. Peripheral smear
  24. 24. Bone marrow
  25. 25. Cytochemistry
  26. 26. Flowcytometry
  27. 27. Cytogenetics
  28. 28. FISH
  29. 29. PCR
  30. 30. Prognosis
  31. 31. Prognostic factors • Age • Initial WBC count • Cytogenetics • Immunologic subtype • Response to initial therapy
  32. 32. Risk groups• Low risk — 92 percent• Standard risk — 82 percent• High risk — 73 percent• Very high risk — 46 percent
  33. 33. Acute lymphoid leukaemia
  34. 34. Acute myeloid leukaemia
  35. 35. Acute myeloid leukaemia
  36. 36. Acute myeloid leukaemia
  37. 37. Treatment
  38. 38. Acute lymphoblastic leukaemia• INDUCTION THERAPY – To eradicate more than 99 percent of the initial burden. – to restore normal hematopoiesis – Usually last for 4-5 weeks• Intensification (consolidation) therapy – High dose methotrexate – Reinduction therapy• CNS targeted therapy – Intrathecal chemo, cranial RT, High Mtx• Maintenance therapy – Oral 6MP and Mtx• Allogenic bone marrow transplantation
  39. 39. Acute myeloid leukaemia• Induction therapy – Cytarabine (7 days) & Daunorubicine (3days)• Consolidation therapy – 3-4 cycles of high dose cytarabine• Autologous and allogenic bone marrow transplantation
  40. 40. Acute myeloid leukaemia
  41. 41. Future
  42. 42. Minimal residual diseaseTechnique and criterion Blasts per 100,000 nucleated cellsStandard microscopy ("complete 5,000remission")Karyotype analysis (20 mitotic 5,000figures)Microscopy, expert 1,000Immunophenotyping: multi- 10parameter flow cytometryColony growth 1Polymerase chain reaction 0.1

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