1. Acute leukemia
- Dr Dinesh Bhurani, DM, FRCPA
Senior bone marrow transplant physician
Rajiv Gandhi Cancer Inst & RC, Delhi

2. ALL
CLL
Lymphomas
MM
naïve
B-lymphocytes
Lymphoid
progenitor
AML
Hematopoietic
stem cell
Myeloid
progenitor
Plasma
cells
T-lymphocytes
Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells

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: multiparameter flow cytometry
10
Colony growth
1
Polymerase chain reaction
0.1