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  • 1. Acute leukemia - Dr Dinesh Bhurani, DM, FRCPA Senior bone marrow transplant physician Rajiv Gandhi Cancer Inst & RC, Delhi
  • 2. ALL MMCLL Lymphomas Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Myeloproliferative disordersAML Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve
  • 3. Incidence
  • 4. Acute myeloid leukaemia
  • 5. ALL
  • 6. Cytopenia
  • 7. Production failure • Stem cell defect – Apastic anaemia • Bone marrow suppression – Drugs – Infections eg malaria, dengue, HIV • Ineffective haemopoiesis – Megaloblastic anaemia – Myelodysplastic syndrome
  • 8. Production failure • Bone marrow infiltration – Haematological malignancy – Non haematological malignancy • Marrow fibrosis – Primary – Secondary • Haemophagocytic syndrome
  • 9. Increased consumption • Hypersplenism • Immune cytopenia
  • 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. Leukaemia • Pancytopenia or bicytopenia – Can it be haematological malignancy? CBC & peripheral smear • Avoid steroids prior to confirmation of diagnosis
  • 12. Bone marrow aspirate and biopsy both are essential.
  • 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. Acute leukaemia • Persistent or progressive lymphadenopathy that does not respond to antibiotic therapy suggests the need for more extensive evaluation.
  • 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. Acute lymphoblastic leukaemia
  • 17. Etiology
  • 18. Leukaemogenesis
  • 19. Leukaemogenesis
  • 20. Classification
  • 21. Acute myeloid leukaemia
  • 22. Diagnosis
  • 23. Peripheral smear
  • 24. Bone marrow
  • 25. Cytochemistry
  • 26. Flowcytometry
  • 27. Cytogenetics
  • 28. FISH
  • 29. PCR
  • 30. Prognosis
  • 31. Prognostic factors • Age • Initial WBC count • Cytogenetics • Immunologic subtype • Response to initial therapy
  • 32. Risk groups • Low risk — 92 percent • Standard risk — 82 percent • High risk — 73 percent • Very high risk — 46 percent
  • 33. Acute lymphoid leukaemia
  • 34. Acute myeloid leukaemia
  • 35. Acute myeloid leukaemia
  • 36. Acute myeloid leukaemia
  • 37. Treatment
  • 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. 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. Acute myeloid leukaemia
  • 41. Future
  • 42. Minimal residual disease Technique and criterion Blasts per 100,000 nucleated cells Standard microscopy ("complete remission") 5,000 Karyotype analysis (20 mitotic figures) 5,000 Microscopy, expert 1,000 Immunophenotyping: multi- parameter flow cytometry 10 Colony growth 1 Polymerase chain reaction 0.1

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