What is the management of blast crisis in Chronic Myeloid Leukemia (CML)?

Management of Blast Crisis in Chronic Myeloid Leukemia

The management of blast crisis in CML requires immediate initiation of induction chemotherapy combined with a tyrosine kinase inhibitor (TKI), followed by allogeneic hematopoietic stem cell transplantation (HSCT) when feasible, as this approach offers the best chance for improved survival and potential cure. 1

Initial Assessment and Treatment Approach

Immediate Management

• Therapy should start immediately upon confirmation of BCR::ABL1 presence 2
• Treatment approach depends on blast crisis phenotype (lymphoid vs. myeloid)
• Begin donor search immediately upon diagnosis of blast crisis 1

Lymphoid Blast Crisis

1. Initial therapy:

   • ALL-type induction chemotherapy combined with TKI 1
   • TKI selection based on mutation profile and prior therapy 1
   • Mandatory prophylactic intrathecal therapy 2, 1

2. Response assessment:

   • Evaluate using morphology, cytogenetics, flow cytometry, and molecular MRD markers including BCR::ABL1 transcripts 2
   • Consider bone marrow aspiration on day 15 to assess early response 2

Myeloid Blast Crisis

1. Initial therapy:

   • AML-type induction chemotherapy following institutional standards 2, 1
   • TKI started at the end of induction (not in parallel with chemotherapy) to avoid excessive toxicity 2, 1

2. Response assessment:

   • Follow response parameters used in AML protocols 2
   • Second cycle of chemotherapy depends on remission status and donor availability 2

CNS Management

Prophylaxis and Treatment

• Intrathecal chemoprophylaxis is mandatory for both lymphoid and myeloid blast crisis 2, 1
• For CNS-1/2 status: Prophylactic approach meeting standards of induction chemotherapy protocol 2
• For CNS-3 status (>5 blasts/μL in CSF): Intensive intrathecal therapy until clearance of blasts 2, 1
• Continue prophylactic intrathecal administration monthly as bridging therapy until transplantation 2

CNS-Directed Radiation

• Consider cranial boost before total body irradiation (TBI) in conditioning regimen if CNS involvement 2, 1
• TBI-based conditioning regimen with cranial boost recommended for patients with CNS involvement 2

Allogeneic Stem Cell Transplantation

Timing and Patient Selection

• Proceed to HSCT ideally within 3 months of achieving second chronic phase 1
• HSCT offers the best chance for cure, with 5-year survival rates significantly better than non-transplant approaches 1
• For patients with lymphoid blast crisis: Transplant after achieving remission with induction therapy 2
• For patients with myeloid blast crisis: Transplant after achieving remission with AML induction 2

Conditioning Regimens

• Reduced intensity conditioning (RIC) may improve non-relapse mortality, overall survival, and relapse-free survival compared to myeloablative conditioning 2
• Consider TBI-based conditioning with cranial boost for patients with CNS involvement 2

Special Considerations

TKI Selection

• For imatinib-naïve patients, imatinib may provide hematologic and cytogenetic benefits 3
• For patients already on imatinib therapy, second or third-generation TKIs are preferred based on mutation profile 1, 4
• Dose adjustments may be necessary:
  • Consider dose reduction or discontinuation in cases of prolonged aplasia after induction 2
  • For chronic phase CML, standard dose is 400 mg/day; for accelerated phase or blast crisis, 600 mg/day 4

Refractory Disease

• For patients with no response to initial therapy or no suitable donor for HSCT, consider:
  • Alternative therapy concepts 2
  • Enrollment in clinical trials with investigational agents 5

Prognosis and Outcomes

• Achievement of second chronic phase, time to transplantation, and presence of additional chromosomal aberrations are key prognostic factors 1
• Without HSCT, remissions are typically short-lived 5, 6
• Quality of life considerations are important when selecting therapy intensity for patients ineligible for transplant 7

Common Pitfalls to Avoid

1. Delaying treatment initiation - therapy should start immediately upon confirmation of blast crisis
2. Neglecting CNS prophylaxis - intrathecal chemotherapy is mandatory
3. Administering TKI concurrently with chemotherapy in myeloid blast crisis - start TKI after completion of induction
4. Delaying donor search - begin immediately upon diagnosis
5. Overtreatment with additional chemotherapy cycles when unnecessary - avoid excessive toxicity when proceeding to HSCT