What is the treatment for blast crisis in chronic myeloid leukemia (CML)?

Treatment of Blast Crisis in Chronic Myeloid Leukemia (CML)

The treatment for blast crisis in CML requires intensive combination therapy with induction chemotherapy appropriate to the blast phenotype (lymphoid or myeloid), tyrosine kinase inhibitors (TKIs), and allogeneic hematopoietic stem cell transplantation (HSCT) as the ultimate goal for eligible patients. 1

Initial Assessment and Classification

• Determine the blast phenotype (lymphoid vs. myeloid) through bone marrow examination, flow cytometry, and molecular studies 1
• Evaluate for CNS involvement with lumbar puncture, as CNS disease is more common in lymphoid blast crisis 1
• Perform BCR-ABL mutation analysis to guide TKI selection 1, 2
• Begin HLA typing for potential transplant candidates immediately 1

Treatment Approach Based on Blast Phenotype

Lymphoid Blast Crisis

• Implement ALL-type induction chemotherapy according to institutional standards combined with a TKI 1
• Start TKI therapy immediately upon confirmation of BCR::ABL1 presence 1
• Administer mandatory prophylactic intrathecal therapy according to ALL protocols 1
• For patients with CNS involvement (CNS-status 3), provide intrathecal chemotherapy according to institutional standards 1
• Consider TBI-based conditioning with cranial boost for patients with CNS involvement proceeding to transplant 1

Myeloid Blast Crisis

• Administer AML-type induction chemotherapy according to national/institutional standards 1
• 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
• For CNS-status 3, provide weekly intrathecal chemotherapy until clearance of blasts 1

TKI Selection

• Choose TKI based on mutation profile 1, 2
• For patients without specific mutations, second-generation TKIs (dasatinib, nilotinib) are preferred over imatinib 3
• Dasatinib has FDA approval for treatment of accelerated or blast phase CML with resistance or intolerance to prior therapy 3
• Consider dasatinib for patients with CNS involvement due to better CNS penetration, though still insufficient as monotherapy for CNS disease 1

Response Assessment and Subsequent Management

• Evaluate response using standards for acute leukemia: morphology, cytogenetics, flow cytometry, and molecular MRD markers 1, 2
• The primary goal is to achieve a second chronic phase (CP) 1, 4, 2
• For patients who achieve second CP:
  • Proceed to allogeneic HSCT ideally within 3 months if a donor is available 1, 2
  • Consider alternative donor sources if a matched donor is unavailable 1
• For patients who fail to achieve second CP:
  • Consider intensification of chemotherapy and use of third-generation TKIs 1
  • Evaluate for experimental treatment concepts 1, 5

Role of Allogeneic Stem Cell Transplantation

• Allogeneic HSCT provides the best chance for long-term survival in blast crisis 2, 6
• Timing is critical - proceed to transplant as soon as second CP is achieved 1, 2
• For patients with CNS involvement, TBI-based conditioning regimen with cranial boost is recommended 1
• Continue monthly prophylactic intrathecal therapy as bridging until transplantation 1

Prognosis and Monitoring

• Despite modern therapies, outcomes in blast crisis remain poor 4, 6, 5
• Most long-term survivors are those who have been successfully transplanted 2
• Regular monitoring for early signs of relapse post-transplant is essential 2, 7

Common Pitfalls to Avoid

• Delaying TKI therapy in lymphoid blast crisis (should start immediately) 1
• Starting TKI therapy concurrently with chemotherapy in myeloid blast crisis (should start after induction) 1
• Neglecting CNS prophylaxis, which is mandatory in both phenotypes 1
• Delaying donor search and transplant evaluation 1, 2
• Underestimating the importance of achieving second CP before transplant 2, 6

The management of blast crisis in CML remains challenging despite advances in TKI therapy. The combination of appropriate induction chemotherapy based on blast phenotype, optimally selected TKI therapy, and timely allogeneic HSCT offers the best chance for improved survival in this difficult clinical scenario.