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Acute Lymphocytic Leukemia (ALL) (Ref. Hari, 18th ed., Pg- 919)
ALL (Working Classification)
L1 Small round blasts with scanty cytoplasm
L2 Pleomorphic larger blasts with more cytoplasm and prominent nucleoli
L3 Vacuolated cytoplasm with vesicular nuclei. 
Clinical Features
  1. ALL is common in children
  2. AML in  middle – aged. 
  3. Onset is abrupt and stormy, and patients present within 3 months of the onset of symptoms. 
  4. Fatigue, anemia, fever (due to infection), bleeding episodes (petechiae, ecchymoses, epistaxis, gum bleeding, fundal haemorrhage) secondary to thrombocytopenia; 
  5. Bone pain and tenderness due to marrow involvement and subperiosteal bone infiltration are seen. 
  6. CNS involvement is due to leukemic infiltration of the meninges, resulting in headache, vomiting, papilledema, cranial nerve palsies etc. 
  7. ALL presents with hepatosplenomegaly and lymphadenopathy. 
  8. Patients are prone to super impose infection by bacteria, HZV, CMV, measles, candidiasis, pneumocystic carinii   
Important Points Pathology of ALL
  1. ALL blasts do not  contain azurophilic granules
  2. ALL blast contain PAS positive material.
  3. Terminal deoxy transferase (TdT) is present in 95% cases.
Classification of Acute lymphoid leukemia (ALL)
Immunologic Subtype % of Cases FAB Subtype Cytogenetic Abnormalities
Pre-B ALL 75 L1, L2 t(9;22), t( 4, 11), t(1; 19)
T Cell ALL 20 L1, L2 14q 11 or 7q34
B Cell ALL 5 L3 t(8; 14), t(8; 22), t(2;8)

Immunophenotypic Classification for ALL
Pre-B Cell Early Pre-B CDI9, CD20-/+, CD10, CD34, TdT
Pre-B CDl9, CD20+/-, CD10, CD34-, clgM, Tdt+/-
B cell B cell CDl9, CD20, CD22, CD10+/-, CD34-, Tdt-, sIg
T cell T cell CD1, CD2, CD3, CD5, CD7, CD10+/-, CD34-/+, Tdt, dual CD4/CD8
Pre B-cell ALL are the commonest types of Acute Lymphoblastic leukemias and account for upto 75% of all ALL Characteristic Features of T cell ALL (20% of ALL)
  1. Occurrence in older children (adolescents) and adult
  2. Predilection for males   
  3. Presence of anterior mediastinal mass in upto half of the cases at presentation (thymic mass) 
  4. Early CNS involvement  (Early dissemination to meninges and testes) 
  5. High WBC count often greater than 100,000/mm3
    The presence of a mediastinal mass in a young adolescent male suggests the diagnosis of precursor T cell ALL. Precursor T cell ALL is phenotypically characterized by an immature T cell phenotype and is positive for TDT and CD7 and may be positive for CD34. 
  1. Anemia (normal or raised MCV)
  2. WBC count: 50,000 – 100,000/μL
  3. Blood film: Shows blast cells and other primitive cells
  4. Bone marrow examination: Hypercellular bone marrow with blasts replacing normal cells to varying degrees (30% or more)
  5. Presence of larger blasts, lower nuclear – cytoplasmic ratio and Auer rods in the cytoplasm of blast cells indicate a myeloblastic type of leukemia
  6. Thrombocytopenia and spontaneous bleeding, especially with platelet count (20,000/L)
Management of ALL
Remission induction CNS prophylaxis
L- Asparaginase
Intrathecal methotrexate (or cytarabine)
Cranial irradiation
Consolidation Maintenance
L – Asparaginase
Combination of intrathecal methotrexate and cranial irradiation for CNS involvement. 
Agents used for intrathecal chemotherapy
  1. Methotrexate
  2. Cytarabine
  3. Thiotepa
Poor Prognostic Factors
  1. High white cell count at presentation (> 100,000/μL)
  2. Male sex
  3. Age <2 or > 10 years
  4. Chromosomal abnormalities
    Philadelphia chromosome (15% of adults) – poor prognosis
    Ph chromosome is most commonly found in non – T, non – B – cell ALL, and is nerve found in T – cell ALL and hence there is a better prognosis in the latter variety
  5. Pre – B – cell ALL with t(1: 19) translocation – poor prognosis
  6. Mature B – cell ALL with t(8 : 14) translocation – very poor prognosis
  7. CNS involvement
  8. L2 and L3 stages.
Good prognostic factors. (LQ 2012)
  1. Low WBC count <50,000/μL
  2. Age 2 -10 yrs (LQ 2012)
  3. Female sex
  4. No dissemination
  5. Hyperdiploidy (LQ 2012)
  6. DNA index >.16
  7. Early pre B cell stage (LQ 2012)
  8. 70% of patients survive for 5 years when they have good prognostic indices (curable)
Hematological evidence of remission.
  1. No evidence of leukemia in blood or bone marrow.
  2. BM blast cell < 5%.

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