Initial Treatment for Blast Crisis in Chronic Myeloid Leukemia
The initial treatment for blast crisis depends critically on blast phenotype: for lymphoid blast crisis, start a tyrosine kinase inhibitor (TKI) immediately upon BCR-ABL confirmation combined with ALL-type induction chemotherapy; for myeloid blast crisis, initiate AML-type induction chemotherapy first, then add TKI at the end of induction to avoid excessive toxicity. 1
Immediate Diagnostic Steps
Before initiating treatment, you must determine the blast phenotype through bone marrow examination, flow cytometry, and molecular studies, as this fundamentally dictates your treatment approach 1. Perform BCR-ABL mutation analysis immediately to guide TKI selection 1, 2. Evaluate for CNS involvement with lumbar puncture, particularly in lymphoid blast crisis where CNS disease is more common 1. Begin HLA typing immediately for all potential transplant candidates to expedite the transplant process 1.
Treatment Based on Blast Phenotype
Lymphoid Blast Crisis
- Start TKI therapy immediately upon confirmation of BCR-ABL1 presence—do not delay 1
- Implement ALL-type induction chemotherapy according to institutional standards combined with the TKI 1, 3
- Administer mandatory prophylactic intrathecal therapy according to ALL protocols to prevent CNS relapse 1
- For patients with documented CNS involvement, provide intrathecal chemotherapy according to institutional standards 1
- Consider dasatinib for patients with CNS involvement due to better CNS penetration, though it remains insufficient as monotherapy for CNS disease 1
Myeloid Blast Crisis
- Initiate AML-type induction chemotherapy first according to national/institutional standards 1, 4
- Standard regimens include cytarabine 100-200 mg/m² continuous infusion for 7 days with daunorubicin 60-90 mg/m² for 3 days or idarubicin 12 mg/m² for 3 days 5
- Start TKI therapy at the end of induction, not concurrently, to avoid excessive toxicity and drug interactions 1
- Include intrathecal prophylaxis according to AML protocols 1
- Choose TKI based on mutation profile to optimize treatment outcomes 1
Critical Timing Considerations
The primary objective is achieving a second chronic phase and proceeding to allogeneic stem cell transplantation ideally within 3 months if a donor is available 1, 2. Allogeneic HSCT provides the best chance for long-term survival in blast crisis, with timing critical to proceed as soon as second chronic phase is achieved 1, 2. For patients with CNS involvement, use a TBI-based conditioning regimen with cranial boost 1. Continue monthly prophylactic intrathecal therapy as bridging until transplantation 1.
Response Assessment
Evaluate response using standards for acute leukemia: morphology, cytogenetics, flow cytometry, and molecular MRD markers 1. Consider alternative donor sources if a matched donor is unavailable to expand transplant options 1.
Common Pitfalls to Avoid
Do not delay TKI therapy in lymphoid blast crisis—it should start immediately upon BCR-ABL1 confirmation, not after chemotherapy 1. Do not start TKI therapy concurrently with chemotherapy in myeloid blast crisis—wait until after induction to avoid compounding toxicity 1. Do not neglect CNS prophylaxis—it is mandatory in both phenotypes regardless of initial CNS involvement 1. Do not delay donor search and transplant evaluation—initiate immediately as most long-term survivors are those who have been transplanted 1, 2.
Prognosis and Realistic Expectations
Despite treatment advances with TKIs, clinical outcomes in blast crisis remain unsatisfactory, with short-lived remissions even with highly potent TKIs 2, 3. Long-term remissions are rare without allogeneic stem cell transplantation 2. The median survival historically has been measured in months, not years, emphasizing the importance of rapid progression to transplant when feasible 4, 6.