What laboratory tests are typically ordered in the event of a blast crisis?

Laboratory Tests for Blast Crisis in Chronic Myeloid Leukemia

The diagnosis of blast crisis in chronic myeloid leukemia requires bone marrow examination with aspirate and biopsy, along with peripheral blood evaluation, supported by flow cytometry, cytogenetic analysis, and molecular genetic testing.

Key Laboratory Tests for Blast Crisis

Complete Blood Count with Differential

• Leukocytosis (often markedly elevated white blood cell count)
• Presence of ≥20% (WHO criteria) or ≥30% (International Bone Marrow Transplant Registry criteria) blasts in peripheral blood 1
• Thrombocytopenia (platelet count <100 × 10^9/L) unrelated to therapy 1
• Anemia (may be severe)
• Basophilia (≥20% in peripheral blood) 1
• Presence of immature granulocytes in peripheral blood

Bone Marrow Examination

• Bone marrow aspirate showing ≥20% (WHO) or ≥30% (International Registry) blasts 1
• Bone marrow biopsy to evaluate for:
  • Large foci or clusters of blasts in the bone marrow 1
  • Fibrosis (which may cause dry tap)
  • Cellularity and architecture

Flow Cytometry

• Essential for determining lineage of blast crisis (myeloid vs. lymphoid)
• Myeloid markers: CD13, CD33, CD117, MPO, CD15, CD65 2
• Lymphoid markers (if B-lymphoid blast crisis): CD19, CD10, CD20, CD22

Cytogenetic Analysis

• Conventional karyotyping to detect:
  • Philadelphia chromosome (t(9;22))
  • Additional chromosomal abnormalities (clonal evolution) 1
  • Minimum of 15 metaphases should be analyzed 1
• FISH analysis if conventional cytogenetics fails

Molecular Genetic Testing

• BCR-ABL1 transcript level quantification 1
• BCR-ABL1 fusion transcript type identification (e13a2, e14a2, e1a2) 1
• Tyrosine kinase domain mutation analysis (critical for treatment decisions) 1
• Next-generation sequencing panel (myeloid or lymphoid depending on phenotype) 1

Additional Important Tests

Biochemistry Panel

• Comprehensive metabolic panel to assess:
  • Liver function (elevated bilirubin, transaminases may occur) 3
  • Renal function
  • Electrolytes (hypokalemia, hyponatremia)
  • Lactate dehydrogenase (often elevated)

Coagulation Studies

• Prothrombin time
• Partial thromboplastin time
• Fibrinogen
• D-dimer (to detect disseminated intravascular coagulation)

Cerebrospinal Fluid Analysis

• Particularly important in lymphoid blast crisis due to higher risk of CNS involvement 4
• Cytology examination for presence of blasts

Interpretation and Clinical Correlation

The laboratory findings must be interpreted in the context of the clinical presentation. Key points to consider:

• Blast crisis is defined by ≥20% blasts (WHO) or ≥30% blasts (International Registry) in blood or bone marrow 1
• Extramedullary blast proliferation also confirms blast crisis diagnosis 1
• Lymphoid blast crisis is more common in patients presenting with de novo blast phase 4
• Myeloid blast crisis is more common in patients with a prior history of chronic phase CML 4

Common Pitfalls to Avoid

1. Failing to distinguish between blast crisis CML and de novo acute leukemia with Philadelphia chromosome
2. Missing additional chromosomal abnormalities that may affect prognosis and treatment
3. Not performing BCR-ABL tyrosine kinase domain mutation analysis, which is critical for TKI selection
4. Overlooking extramedullary sites of disease (CNS, lymph nodes, skin)
5. Relying solely on peripheral blood analysis without bone marrow examination

Early and accurate diagnosis of blast crisis is crucial as it significantly impacts morbidity and mortality outcomes, with allogeneic stem cell transplantation offering the best chance for long-term survival 5.