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
- scant cytoplasm
- few, small nucleoli
- no granules and/or Auer rods
- positive for PAS and/or TdT (terminal deoxynucelotidyl transferase)
• Immunophenotypic classification of ALL à - Pro-B-cell ALL à TdT +, CD 19 +, CD 10 (CALLA) –
- Pre-B-cell ALL à TdT +, CD 19 +, CD 10 +, cytoplasmic Ig +
- Mature B-cell (Burkitt) ALL àTdT -, CD 19 +, surface Ig +
- Pre-T-cell ALL à TdT +, CD 3 -, CD4+/CD8+ or CD4-/CD8-
- 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: - Induction therapy àvincristine, prednisone, daunorubicin and Lasparaginase
- Consolidation therapy àcytarabine + daunorubicin
- Maintenance therapy à2-3 years of methotrexate and/or 6-
marcaptopurine (most commonly used agents) - CNS prophylaxis àintrathecal methotrexate
- Relapse after complete remission à intensive chemotherapy + BMT
- Relapse at “sanctuary” sites (e.g. CNS, testes) àradiation
- Complete remission in ALL with t(9;22) or t(4;11) àBMT
- Initial therapy of ALL with t(9;22) à Hyper-CVAD regimen
(cyclophosphamide, vincristine, Adriamycin, dexamethasone) ± imatinib - Supportive measures
• Poor prognostic factors àage < 2 or > 10, male sex, black race, ↑ WBC count,
mature phenotype, mediastinal mass, T-cell origin, chromosomal translocations
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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: - Stage 0 à lymphocytosis
- Stage 1 àlymphocytosis + lymphadenopathy
- Stage 2 àlymphocytosis + lymphadenopathy + splenomegaly
- Stage 3 àlymphocytosis + anemia (excluding autoimmune etiology)
- Stage 4 àlymphocytosis + thrombocytopenia
• Management: - Stages 0-2 + asymptomatic àobservation
- Symptomatic and/or Stages 3-4 àfludarabine ± rituximab (side effects à
myelosuppression and immunosuppression, requiring PCP prophylaxis) - Alternative for older individuals à chlorambucil ± prednisone
- Relapse/failure àpentostatin, alemtuzumab (anti-CD52 monoclonal antibody)
or bendamustine - 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: - Asymptomatic + normal/mildly decreased CBC à observation
- Best initial therapy àcladribine or pentostatin
- Relapse/failure àrituximab (or alemtuzumab)
• Most common cause of mortality à infections