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Tuesday, July 9, 2013

Acute lymphoblastic leukemia (ALL)

Clonal proliferation and accumulation of blast cells from lymphoid series in blood, bone marrow and other organs

Disorder  originates in single B or T lymphocyte progenitor 

B cell type – 80%     T cell type – 20%
Common age group – 5 to 15 yrs
Etiology  - unknown 

Acute leukemias - clinical features

1. Bleeding
2. Fever/infection
3. Fatiguability and pallor
4. Hepatomegaly
5. Splenomegaly
6. Lymphadenopathy
7. CNS involvement
8. Testicular involvement in males


Acute leukemias - laboratory findings 

1. Blood examination - anemia, - thrombocytopenia, - variable leukocyte count, usually increased from 10,000 to 500,000/cmm - blood morphology: presence of blast cells 

2. Bone marrow morphology - presence of blast cells (>20%) - suppression of normal hematopoiesis
3. Cytochemical stains
4. Immunophenotyping
5. Cytogenetics

Immune phenotyping
Cytogenetics
Morphologic subtypes of acute lymphoblastic leukemias  (FAB classification)

Subtype           Morphology       Occurrence (%)
L1   Small round blasts              75
clumped chromatin
L2 Pleomorphic larger blasts     20
clefted nuclei, fine chromatin
L3 Large blasts, nucleoli,       5

vacuolated cytoplasm

Chromosomal/molecular abnormalities with prognostic significance in ALL

Better prognosis
- normal karyotype
- hyperdiploidy
Poor prognosis
- t (8; 14)
- t (4; 11)
Very poor prognosis
- t (9; 22); BCR/ABL (+)


 Treatment strategy in ALL

Remission induction therapy in ALL

1. Antineoplastic treatment
a.Drugs: L-asparaginase, Daunorubicin, Prednisolone, Vincristine
    b/Treatment duration: 4-8 weeks
c/ No of courses: 1- 2
2. CNS prophylaxis – Methotrexate (intrathecal)
3. Supportive care

4. Treatment of complications

Consolidation

Drugs – Etoposide, cytarabine, and Daunorubicn, Methotrexate(I.v.)
+/-

Stem Cell transplantation

Maintenance of remission


  • Prednisolone, Vincristine, Mercaptopurine and Methotrexate (oral)
  • May need to be continued for 2-3 years



Treatment results in ALL 

Adults
Complete remission  (CR) 80-85%
Leukemia-free survival (LFS)            30-40%

Children
Complete remission (CR) 95-99%
Leukemia-free survival (LFS)            70-80%

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