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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

naïve
B-lymphocytes

Lymphoid
progenitor

AML
Hematopoietic
stem cell

Myeloid
progenitor

Plasma
cells
T-lymphocytes

Myeloproliferative disorders
Neutrophils
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
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

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