From the Guidelines
Blast crisis in leukemia is a life-threatening condition characterized by the rapid progression of chronic myeloid leukemia (CML) to an aggressive acute leukemia, known as blast phase (BP), which may be of myeloid, lymphoid, or mixed phenotype.
Workup and Diagnosis
The diagnosis of blast crisis rests on the percentage of blasts (20% or 30%) in blood or marrow, and flow cytometry distinguishes between lymphoid and myeloid BP, allowing for appropriate selection of treatment 1.
- Early indicators of progression include the appearance of additional cytogenetic abnormalities (ACA), somatic mutations, and clinical deterioration without obvious explanation.
- KD-mutation analysis is also crucial in guiding treatment decisions.
Treatment Options
Treatment of blast crisis typically involves intensive combination chemotherapy with or without a tyrosine kinase inhibitor (TKI) in preparation for a prompt allogeneic hematopoietic stem cell transplant (allo-SCT) if possible 1.
- For patients with lymphoid BP, an ALL-type induction therapy is recommended, whereas for those with myeloid BP, an AML-type induction therapy is appropriate.
- Dasatinib or nilotinib, followed by allo-SCT, is recommended for disease progression to accelerated-phase or blast phase after imatinib therapy 1.
- In patients who cannot tolerate intensive chemotherapy regimens, a more palliative approach with less intensive therapy according to immunophenotype should be considered.
- The addition of imatinib or dasatinib to chemotherapy has been shown to improve outcome in patients with de novo or minimally treated Ph-positive ALL 1.
- Allogeneic HSCT currently remains the primary curative intervention for CML-BP, and recommendations for the timing of transplantation, donor and graft selection, selection of a conditioning regimen, and prophylaxis for graft-versus-host disease are crucial 1.
Prognosis and Management
Once blast crisis has occurred, survival is generally less than 1 year with death due to infection or bleeding 1.
- Management according to treatment recommendations is intended to provide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease 1.
- Intrathecal chemoprophylaxis is important for patients with CML-BP lymphoid phenotype, and the optimal number and choice of drugs remain unclear 1.
- Post-transplant TKI therapy and management of molecular relapse are also essential components of the treatment plan 1.
From the Research
Definition and Biology of Blast Crisis
- Blast crisis (BC) is a major therapeutic challenge in the management of chronic myeloid leukemia (CML) 2, 3, 4, 5
- BC can be myeloid, lymphoid, or mixed lineage, with myeloid BC being the most common type 2
- BC in CML is mediated by aberrant tyrosine kinase activity of the BCR::ABL fusion protein 2
- The introduction of BCR::ABL tyrosine kinase inhibitors (TKIs) has reduced the incidence of BC 2, 3
Workup and Treatment Options
- The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and proceed to an allogeneic stem cell transplantation (SCT) in eligible patients 3, 4, 5
- Treatment with TKIs has improved survival in BC modestly, but most long-term survivors are those who have been transplanted 4
- Patients in BC should be treated with a TKI according to mutation profile, with or without chemotherapy, with the goal of achieving a second CP and proceeding to allogeneic SCT as quickly as possible 4
- Allogeneic SCT provides the best chance of a cure in BC, and should be offered to all patients eligible for this procedure 6, 4, 5
Outcomes and Prognosis
- The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short-lived 3
- Outcomes remain dismal, with a median overall survival of 23.8 months (median follow-up 27.8 months) 6
- De novo BC and BC evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities 6