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Acute leukemia
- Dr Dinesh Bhurani, DM, FRCPA
  Senior bone marrow transplant physician
  Rajiv Gandhi Cancer Inst & RC, Delhi
ALL   CLL       Lymphomas        MM
                              naĂŻve


                               B-lymphocytes

                                                         Plasma
                Lymphoid                                  cells
                progenitor               T-lymphocytes


                        AML    Myeloproliferative disorders
Hematopoietic   Myeloid                Neutrophils
stem cell       progenitor

                                       Eosinophils


                                       Basophils


                                       Monocytes


                                       Platelets


                                       Red cells
Incidence
Acute myeloid leukaemia
ALL
Cytopenia
Production failure
• Stem cell defect
  – Apastic anaemia
• Bone marrow
  suppression
  – Drugs
  – Infections eg malaria, dengue,
    HIV
• Ineffective
  haemopoiesis
  – Megaloblastic anaemia
  – Myelodysplastic syndrome
Production failure
• Bone marrow infiltration
  – Haematological malignancy
  – Non haematological malignancy
• Marrow fibrosis
  – Primary
  – Secondary
• Haemophagocytic syndrome
Increased consumption


• Hypersplenism
• Immune cytopenia
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
Leukaemia

• Pancytopenia or bicytopenia – Can it be
  haematological malignancy? CBC &
  peripheral smear
• Avoid steroids prior to confirmation of
  diagnosis
Bone marrow aspirate and
biopsy both are essential.
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
Acute leukaemia

• Persistent or progressive lymphadenopathy
  that does not respond to antibiotic therapy
  suggests the need for more extensive
  evaluation.
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
Acute lymphoblastic leukaemia
Etiology
Leukaemogenesis
Leukaemogenesis
Classification
Acute myeloid leukaemia
Diagnosis
Peripheral smear
Bone marrow
Cytochemistry
Flowcytometry
Cytogenetics
FISH
PCR
Prognosis
Prognostic factors
 •   Age
 •   Initial WBC count
 •   Cytogenetics
 •   Immunologic subtype
 •   Response to initial therapy
Risk groups
•   Low risk — 92 percent
•   Standard risk — 82 percent
•   High risk — 73 percent
•   Very high risk — 46 percent
Acute lymphoid leukaemia
Acute myeloid leukaemia
Acute myeloid leukaemia
Acute myeloid leukaemia
Treatment
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
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
Acute myeloid leukaemia
Future
Minimal residual disease
Technique and criterion          Blasts per 100,000 nucleated cells

Standard microscopy ("complete
                                 5,000
remission")
Karyotype analysis (20 mitotic
                                 5,000
figures)
Microscopy, expert               1,000
Immunophenotyping: multi-
                                 10
parameter flow cytometry
Colony growth                    1
Polymerase chain reaction        0.1

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ALL

  • 1. Acute leukemia - Dr Dinesh Bhurani, DM, FRCPA Senior bone marrow transplant physician Rajiv Gandhi Cancer Inst & RC, Delhi
  • 2. ALL CLL Lymphomas MM naĂŻve B-lymphocytes Plasma Lymphoid cells progenitor T-lymphocytes AML Myeloproliferative disorders Hematopoietic Myeloid Neutrophils stem cell progenitor Eosinophils Basophils Monocytes Platelets Red cells
  • 5. ALL
  • 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
  • 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
  • 28. FISH
  • 29. PCR
  • 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
  • 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
  • 42. Minimal residual disease Technique and criterion Blasts per 100,000 nucleated cells Standard microscopy ("complete 5,000 remission") Karyotype analysis (20 mitotic 5,000 figures) Microscopy, expert 1,000 Immunophenotyping: multi- 10 parameter flow cytometry Colony growth 1 Polymerase chain reaction 0.1