Treatment of chronic myeloid leukemia in accelerated phase
- 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/or 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 used in the treatment of CML. Since then, several other tyrosine kinase inhibitors have been developed and tested in 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. As advances are made 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. Interestingly, some patients progress to blast crisis without a clinically discernible accelerated phase. This is supported by an analysis of gene expression profiles in different stages of CML demonstrated relatively distinct patterns in chronic and blast phases without an identifiable "signature" of accelerated phase suggesting that CML is biologically more likely to be a "bi" rather than a triphasic disease .
The treatment of CML in accelerated phase is discussed here. The treatment of CML in chronic phase or blast crisis is discussed separately as is the use of hematopoietic cell transplantation. (See "Treatment of chronic myeloid leukemia in blast crisis" 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".)
DEFINITION OF ACCELERATED PHASE DISEASE
Varying definitions have been applied to the accelerated phase of CML (table 1) . The most frequently used criteria from the World Health Organization (WHO) define the accelerated phase in patients with CML by the presence of one or more of the following features:
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