What are the different classifications of leukemia and their corresponding treatments?

Leukemia Classification and Treatment Approaches

Leukemia is classified into four major categories based on cell lineage and disease progression, with treatment strategies tailored to specific molecular and genetic characteristics of each subtype. 1

Major Classifications of Leukemia

1. Acute Myeloid Leukemia (AML)

• Definition: Characterized by rapid proliferation of immature myeloid cells (blasts) in bone marrow (≥20% blasts)

• Subclassification: 1

  • AML with recurrent genetic abnormalities:
    • AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
    • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
    • Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA
    • AML with t(9;11)(p22;q23); MLLT3-MLL
    • AML with other specific translocations
  • AML with myelodysplasia-related changes
  • Therapy-related myeloid neoplasms
  • AML, not otherwise specified
    • Various morphological subtypes (e.g., with minimal differentiation, without maturation)

• Treatment approach:

  • Standard induction: Cytarabine + anthracycline ("7+3" regimen)
  • For APL: All-trans retinoic acid (ATRA) + arsenic trioxide
  • For specific genetic subtypes: Targeted therapies
  • Consolidation therapy and consideration for stem cell transplantation in high-risk patients 2

2. Acute Lymphoblastic Leukemia (ALL)

• Definition: Rapid proliferation of immature lymphoid cells

• Subclassification: 1

  • B-lymphoblastic leukemia/lymphoma:
    • B-ALL with recurrent genetic abnormalities (e.g., t(9;22), t(12;21))
    • B-ALL, NOS
  • T-lymphoblastic leukemia/lymphoma

• Treatment approach:

  • Induction therapy with multi-agent regimens (vincristine, corticosteroids, anthracyclines)
  • For Ph+ ALL: Addition of tyrosine kinase inhibitors
  • CNS prophylaxis
  • Consolidation, interim maintenance, delayed intensification, and maintenance therapy
  • Consideration for stem cell transplantation in high-risk patients 1

3. Chronic Myeloid Leukemia (CML)

• Definition: Clonal myeloproliferative disorder characterized by the Philadelphia chromosome t(9;22)(q34;q11) resulting in BCR-ABL1 fusion gene

• Phases: 1, 3

  • Chronic phase: <10% blasts in blood/bone marrow
  • Accelerated phase: 10-29% blasts, >20% basophils
  • Blast crisis: ≥30% blasts

• Treatment approach:

  • First-line: Tyrosine kinase inhibitors (TKIs) like imatinib 400mg daily 3, 4
  • Regular monitoring of molecular response (BCR-ABL1 transcripts)
  • For TKI failure: Alternative TKIs or stem cell transplantation
  • 5-year survival rate with TKI therapy: approximately 90% 3

4. Chronic Lymphocytic Leukemia (CLL)

• Definition: Monoclonal expansion of small, mature B lymphocytes (≥5 × 10^9/L B lymphocytes) 1
• Diagnosis: Flow cytometry showing characteristic immunophenotype
• Treatment approach:
  • Asymptomatic early-stage: Observation ("watch and wait")
  • Treatment indications: Progressive bone marrow failure, massive/symptomatic splenomegaly, progressive lymphocytosis, constitutional symptoms
  • Treatment options: Chemoimmunotherapy, BTK inhibitors, BCL-2 inhibitors 1

Diagnostic Approach

1. Complete blood count and peripheral blood smear

   • Leukocytosis, anemia, thrombocytopenia
   • Presence of blast cells or abnormal cells

2. Bone marrow examination

   • Aspirate and biopsy for morphology
   • Cellularity and blast percentage
   • Dysplastic features

3. Immunophenotyping (flow cytometry)

   • Essential for lineage determination (myeloid vs. lymphoid)
   • Further subclassification (B vs. T cell in ALL) 1

4. Cytogenetic analysis

   • Karyotyping for chromosomal abnormalities
   • FISH for specific translocations
   • Prognostic significance

5. Molecular studies

   • PCR for fusion genes (BCR-ABL1, PML-RARA)
   • Gene mutations (NPM1, CEBPA, FLT3, etc.)

Treatment Principles by Leukemia Type

For Acute Leukemias (AML and ALL):

1. Induction therapy to achieve complete remission
2. Consolidation therapy to eliminate residual disease
3. Maintenance therapy (especially in ALL)
4. Stem cell transplantation for high-risk patients

For Chronic Leukemias (CML and CLL):

1. Targeted therapy (TKIs for CML)
2. Observation for asymptomatic early-stage disease
3. Treatment when disease progresses or becomes symptomatic
4. Regular monitoring for disease progression

Important Considerations

• Age and comorbidities significantly impact treatment decisions and outcomes
• Genetic/molecular profile is crucial for risk stratification and treatment selection
• Minimal residual disease (MRD) monitoring guides treatment decisions
• Supportive care (infection prevention, transfusion support) is essential

Common Pitfalls to Avoid

1. Misclassification: Ensure proper immunophenotyping and molecular testing before initiating therapy
2. Delayed diagnosis: Prompt referral to hematology-oncology is essential for suspected leukemia
3. Inadequate monitoring: Regular assessment of treatment response is critical
4. Overlooking complications: Be vigilant for tumor lysis syndrome and infections during treatment
5. Insufficient supportive care: Prophylactic antibiotics and transfusion support are often necessary

Untreated acute leukemia is uniformly fatal with median survival of less than 3 months, highlighting the importance of prompt diagnosis and appropriate treatment 2.