Acute Lymphoblastic Leukemia/Lymphoma (ALL)

Most common leukemia in children
• Boys > girls
• Whites > African-Americans
• 85% of cases are of B-cell origin
• Risk factors àradiation, benzene, genetic syndromes (e.g. Down syndrome, Bloom
syndrome, etc.)
• Clinical features à symptoms/signs of anemia, thrombocytopenia and/or neutropenia,
↑ temperature, severe bone pain, arthralgias, lymphadenopathy, splenomegaly ±
hepatomegaly, mediastinal mass (especially with T-cell ALL) ± respiratory distress,
possible CNS disease, testicular enlargement and/or tissue infiltration
• Lab findings àpancytopenia with ↓ reticulocyte count, circulating lymphoblasts, ↑
LDH, ↑ uric acid
• Most accurate diagnostic test in general àbore marrow biopsy showing > 20%
marrow blasts
• Most accurate diagnostic test to differentiate between AML and ALL and/or different
forms of ALL àimmunophenotypic and/or cytogenetic analysis
• Characteristics of a lymphoblast à

  1. scant cytoplasm
  2. few, small nucleoli
  3. no granules and/or Auer rods
  4. positive for PAS and/or TdT (terminal deoxynucelotidyl transferase)
    • Immunophenotypic classification of ALL à
  5. Pro-B-cell ALL à TdT +, CD 19 +, CD 10 (CALLA) –
  6. Pre-B-cell ALL à TdT +, CD 19 +, CD 10 +, cytoplasmic Ig +
  7. Mature B-cell (Burkitt) ALL àTdT -, CD 19 +, surface Ig +
  8. Pre-T-cell ALL à TdT +, CD 3 -, CD4+/CD8+ or CD4-/CD8-
  9. Mature T-cell ALL à CD 3 +. CD4+/CD8 – or CD4+/CD8+
    • Common genetic abnormalities (associated with poor prognosis) àt(4;11), t(9;22),
    t(8;14), t(1;19)
    • Management:
  10. Induction therapy àvincristine, prednisone, daunorubicin and Lasparaginase
  11. Consolidation therapy àcytarabine + daunorubicin
  12. Maintenance therapy à2-3 years of methotrexate and/or 6-
    marcaptopurine (most commonly used agents)
  13. CNS prophylaxis àintrathecal methotrexate
  14. Relapse after complete remission à intensive chemotherapy + BMT
  15. Relapse at “sanctuary” sites (e.g. CNS, testes) àradiation
  16. Complete remission in ALL with t(9;22) or t(4;11) àBMT
  17. Initial therapy of ALL with t(9;22) à Hyper-CVAD regimen
    (cyclophosphamide, vincristine, Adriamycin, dexamethasone) ± imatinib
  18. Supportive measures
    • Poor prognostic factors àage < 2 or > 10, male sex, black race, ↑ WBC count,
    mature phenotype, mediastinal mass, T-cell origin, chromosomal translocations
    21
    Chronic Lymphocytic Leukemia/Small Cell Lymphoma (CLL/SCL)
    • Clonal proliferation of mature B lymphocytes
    • Most common form of leukemia
    • Age > 50
    • Males > Females
    • Clinical features àasymptomatic (most common; e.g. detected on routine CBC, etc.)
    to fatigue, splenomegaly, lymphadenopathy, ↑ risk of infections, ± symptoms/signs of
    anemia and/or thrombocytopenia
    • Complications àautoimmune hemolytic anemia, immune-mediated
    thrombocytopenia, hypogammaglobulinemia, Richter syndrome (transformation to
    high-grade large-cell lymphoma)
    • Lab findings à ↑ WBC count with absolute lymphocytosis (lymphocyte count >
    5000/µL) ± ↓ RBC and/or platelet counts
    • Blood smear àsmall, mature lymphocytes + “smudge” cells
    • Bone marrow biopsy à> 30% lymphocytes
    • Most accurate diagnostic test àflow-cytometry (CD5+, CD19+, CD20+ and CD23+)
    • Staging:
  19. Stage 0 à lymphocytosis
  20. Stage 1 àlymphocytosis + lymphadenopathy
  21. Stage 2 àlymphocytosis + lymphadenopathy + splenomegaly
  22. Stage 3 àlymphocytosis + anemia (excluding autoimmune etiology)
  23. Stage 4 àlymphocytosis + thrombocytopenia
    • Management:
  24. Stages 0-2 + asymptomatic àobservation
  25. Symptomatic and/or Stages 3-4 àfludarabine ± rituximab (side effects à
    myelosuppression and immunosuppression, requiring PCP prophylaxis)
  26. Alternative for older individuals à chlorambucil ± prednisone
  27. Relapse/failure àpentostatin, alemtuzumab (anti-CD52 monoclonal antibody)
    or bendamustine
  28. immune-mediated hemolytic anemia and/or thrombocytopenia àsteroids
    Hairy Cell Leukemia
    • A mature B-cell neoplasm
    • Males > Females; middle age
    • Clinical features àasymptomatic to splenomegaly, progressive fatigue,
    symptoms/signs of anemia, thrombocytopenia and/or neutropenia
    • In summary àtriad of middle age, splenomegaly and pancytopenia
    • Lab findings à consistent with pancytopenia
    • Blood smear à WBCs with “hair-like” cytoplasmic projections
    • Bone marrow aspirate à“dry tap”
    • Most accurate diagnostic test à bone marrow biopsy positive for TRAP (tartrateresistant
    acid phosphatase) stain
    • Flow Cytometry àCD19+, CD20+, CD11+, CD25+
    • Management:
  29. Asymptomatic + normal/mildly decreased CBC à observation
  30. Best initial therapy àcladribine or pentostatin
  31. Relapse/failure àrituximab (or alemtuzumab)
    • Most common cause of mortality à infections