Treatment of chronic myeloid leukemia in blast crisis
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t(9;22)(q34;q11) and the BCR-ABL fusion gene. This genetic abnormality results in the formation of a unique gene product (BCR-ABL), which results in a constitutively active tyrosine kinase. It is this deregulated tyrosine kinase that is implicated in the development of CML and is the target of current therapies. (See "Molecular genetics of chronic myeloid leukemia".)
Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) used in the treatment of CML. Since then, several other TKIs have been developed for the treatment of patients with CML, most notably dasatinib, nilotinib, bosutinib, and ponatinib. (See "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia".)
CML has historically been a triphasic disease. Approximately 85 to 90 percent of patients present in a chronic stable phase. Without treatment, this inevitably progresses to a more aggressive, accelerated phase, and then culminates in a very difficult to treat blast crisis. With advances in the treatment of chronic phase CML, fewer patients (approximately 6 percent at five years) are progressing to accelerated phase and blast crisis. In addition, 10 to 15 percent of patients will initially present in accelerated phase or blast crisis.
The treatment of CML in blast crisis is discussed here. The treatment of CML in chronic or accelerated phase is discussed separately, as is the use of hematopoietic cell transplantation (HCT). (See "Treatment of chronic myeloid leukemia in accelerated phase" and "Overview of the treatment of chronic myeloid leukemia" and "Initial treatment of chronic myeloid leukemia in chronic phase" and "Treatment of chronic myeloid leukemia in chronic phase after failure of initial therapy" and "Hematopoietic cell transplantation in chronic myeloid leukemia".)
In approximately 30 percent of cases, blast crisis in CML is of the lymphoid (ie, acute lymphoblastic leukemia [ALL]), rather than the myeloid (ie, acute myeloid leukemia [AML]) phenotype. TKIs can be incorporated into a treatment plan for these and other patients with Philadelphia chromosome positive ALL. This is discussed separately. (See "Induction therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults", section on 'TKI plus chemotherapy'.)
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- DEFINITION OF BLAST CRISIS
- EVALUATION UPON TRANSFORMATION
- REMISSION INDUCTION
- Lymphoid blast crisis
- Myeloid blast crisis
- Choice of TKI
- - Imatinib
- - Dasatinib
- - Nilotinib
- - Bosutinib
- - Ponatinib
- RESPONSE EVALUATION
- POST-REMISSION THERAPY
- Assessing HCT eligibility
- Eligible for HCT
- Ineligible for HCT
- TREATMENT AFTER FAILURE OF INITIAL THERAPY
- CLINICAL TRIALS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS