What are the different types of Leukemia (Leukemia)?

Types of Leukemia

Leukemia is classified into four major categories based on cell lineage (myeloid or lymphoid) and disease progression (acute or chronic), with specific molecular and genetic characteristics determining treatment approaches and prognosis. 1

Acute Myeloid Leukemia (AML)

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

• Classification: According to WHO 2008 classification 2:

  • AML with recurrent genetic abnormalities
  • AML with myelodysplasia-related changes
  • Therapy-related myeloid neoplasms
  • AML, not otherwise specified (NOS)
  • Myeloid sarcoma
  • Myeloid proliferations related to Down syndrome

• Key genetic subtypes:

  • AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
  • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
  • APL with t(15;17)(q22;q12); PML-RARA (acute promyelocytic leukemia)
  • AML with mutations in NPM1, CEBPA, FLT3 2

• Treatment approach: Induction with cytarabine and anthracycline, followed by consolidation therapy and possibly stem cell transplantation for high-risk patients 2

Acute Lymphoblastic Leukemia (ALL)

• Definition: Rapid proliferation of immature lymphoid cells

• Classification:

  • B-lymphoblastic leukemia/lymphoma
  • T-lymphoblastic leukemia/lymphoma
  • Mixed phenotype acute leukemia 2

• Immunophenotypic subtypes:

  • Pre-pre-B-cell (pro-B-cell) ALL: TdT+, CD19/CD22/CD79a+, CD10-
  • Common B-cell ALL: CD10+
  • Pre-B-cell ALL: Cytoplasmic immunoglobulins+, CD10/CD19/CD22/CD79a+
  • Mature B-cell ALL: Surface immunoglobulins+, TdT- 2
  • T-cell ALL: Cytoplasmic CD3 or surface CD3, CD1a/CD2/CD5/CD7 (variable)

• Treatment approach: Multi-agent regimens including CNS prophylaxis, consolidation, interim maintenance, delayed intensification, and maintenance therapy 1

Chronic Myeloid Leukemia (CML)

• Definition: Clonal myeloproliferative disorder characterized by the Philadelphia chromosome t(9;22)(q34;q11) resulting in BCR-ABL1 fusion gene 2

• Classification by phase:

  • Chronic phase
  • Accelerated phase
  • Blast crisis (transformation to acute leukemia)

• Treatment approach: Tyrosine kinase inhibitors (TKIs) like imatinib as first-line therapy, with regular monitoring of molecular response 1

Chronic Lymphocytic Leukemia (CLL)

• Definition: Monoclonal expansion of small, mature B lymphocytes (≥5 × 10^9/L B lymphocytes) 2

• Diagnostic criteria:

  • ≥5000 B lymphocytes/μl in peripheral blood for at least 3 months
  • Clonality confirmed by flow cytometry
  • Cells co-express CD5, CD19, CD20, CD23
  • Low levels of surface immunoglobulin, CD20, and CD79b 2

• Staging systems:

  • Binet staging (A, B, C)
  • Rai staging (0-IV) 2

• Treatment approach: Observation for asymptomatic early-stage disease; treatment indicated for progressive bone marrow failure, symptomatic splenomegaly, progressive lymphocytosis, or constitutional symptoms 1

Diagnostic Approach

1. Complete blood count and peripheral blood smear: Essential initial tests
2. Bone marrow examination: Aspirate and biopsy to determine leukemia subtype
3. Immunophenotyping: Flow cytometry for lineage determination
4. Cytogenetic analysis: Karyotyping and FISH for chromosomal abnormalities
5. Molecular studies: PCR for fusion genes and mutations 1

Prognostic Factors

• Age: Younger patients generally have better outcomes
• Genetic/molecular profile: Certain mutations or chromosomal abnormalities predict better or worse outcomes
• Response to initial therapy: Early response correlates with better long-term outcomes
• Minimal residual disease (MRD): Lower MRD levels after treatment correlate with better outcomes 2, 1

Common Pitfalls in Diagnosis and Management

• Misclassification: Incorrect classification can lead to inappropriate treatment
• Delayed diagnosis: Early symptoms are often nonspecific (fatigue, fever, weight loss)
• Overlooking genetic factors: Genetic testing is essential for risk stratification
• Inadequate monitoring: Regular assessment of treatment response is crucial 1, 3

Long-term Complications

• Secondary malignancies: Increased risk after chemotherapy or radiation
• Cardiovascular disease: Particularly after anthracycline therapy
• Endocrine disorders: Including metabolic syndrome, hypothyroidism, and hypogonadism
• Immunosuppression: Increased risk of serious infections 3, 4

Leukemia classification continues to evolve with advances in molecular diagnostics, leading to more personalized treatment approaches based on specific genetic and molecular characteristics of each subtype.