What is the recommended management for blast crisis?

Management of Blast Crisis in Chronic Myeloid Leukemia

The recommended management for blast crisis in CML includes induction chemotherapy combined with a tyrosine kinase inhibitor (TKI), followed by allogeneic hematopoietic stem cell transplantation (HSCT) when feasible. 1

Initial Assessment and Classification

• Determine blast crisis phenotype (lymphoid vs. myeloid) through:

  • Bone marrow examination with flow cytometry
  • Cytogenetics and molecular testing for BCR-ABL mutations
  • Assessment of extramedullary involvement

• Evaluate for CNS involvement:

  • Lumbar puncture for CSF analysis
  • CNS status classification:
    • CNS-1: No blasts in CSF
    • CNS-2: <5 blasts/μL in CSF
    • CNS-3: ≥5 blasts/μL in CSF

Treatment Algorithm Based on Blast Phenotype

Lymphoid Blast Crisis

1. Initial Therapy:

   • ALL-type induction chemotherapy + TKI 1
   • TKI selection based on mutation profile
   • Mandatory prophylactic intrathecal therapy

2. CNS Management:

   • For CNS-1/2: Prophylactic intrathecal chemotherapy per institutional protocol
   • For CNS-3: Intensive intrathecal therapy until clearance of blasts
   • Consider cranial boost before TBI in conditioning regimen if CNS involvement 1

3. Response Evaluation:

   • Assess for achievement of second chronic phase
   • Proceed to HSCT if donor available

Myeloid Blast Crisis

1. Initial Therapy:

   • AML-type induction chemotherapy + TKI 1
   • Start TKI at the end of induction (not concurrently) to avoid excessive toxicity 1
   • Intrathecal prophylaxis per AML protocol

2. Response Evaluation:

   • Follow response parameters used in AML protocols
   • Consider second cycle of chemotherapy based on remission status and donor availability

Hematopoietic Stem Cell Transplantation

• Donor Search: Begin immediately upon diagnosis of blast crisis

  • Matched sibling donor (MSD)
  • Matched unrelated donor (MUD) with HLA ≥9/10 match

• Timing: Proceed to HSCT ideally within 3 months of achieving second chronic phase 1

• If No Donor Available:

  • Consider alternative donor sources (haploidentical, cord blood)
  • Continue TKI with monthly response evaluation
  • Consider experimental treatment concepts

Treatment Considerations and Pitfalls

• TKI Selection:

  • Second or third-generation TKIs preferred
  • Base selection on prior therapy and mutation profile
  • Dasatinib has better CNS penetration but still insufficient for CNS disease treatment 1

• Common Pitfalls:

  1. Delayed HSCT: Missing the window of second chronic phase significantly worsens outcomes
  2. Inadequate CNS prophylaxis: CNS relapse can occur despite systemic control
  3. Excessive toxicity: Balance between aggressive therapy and treatment-related mortality

• Prognosis Factors:

  • Achievement of second chronic phase
  • Time to transplantation
  • Presence of additional chromosomal aberrations

Long-term Outcomes

Despite advances in therapy, blast crisis remains challenging with limited long-term survival. Allogeneic HSCT offers the best chance for cure, with 5-year survival rates of approximately 10% for patients in blast crisis compared to 75% for those in chronic phase 1, 2.

The primary goal is to achieve a second chronic phase and proceed to transplantation as quickly as possible, as remissions are typically short-lived even with potent TKIs 3, 2.