Perspectives on the future of chronic myeloid leukemia treatment

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Chronic myeloid leukemia (CML) is probably the best understood human malignancy at the molecular level, but among the hardest to explain to patients concerning appropriate treatment options. At present, we do not know the long-term outcome of promising new therapies such as the tyrosine kinase inhibitor imatinib mesylate (Gleevec ™, Novartis Pharmaceuticals Corp, East Hanover, NJ) (formerly STI571) and nonmyeloablative transplants. There is also no reliable way to predict which patients will respond to a particular therapy. The development of methods to predict therapeutic response will be of major benefit to patients, and the newly emerging science of gene array analysis may provide such a tool. In this context, given the proven likelihood of cure with allogeneic transplantation and the negative effects of delay, in Seattle we continue to suggest transplantation as the initial form of therapy for patients below age 55 years with matched sibling donors. For patients without matched donors below the age of 40, we would suggest an unrelated donor search and only proceed directly to transplant for those with allele-level matches. For younger patients without matches and those aged 40 to 55, an initial trial of imatinib mesylate might be preferred. For patients over age 55 with CML, initial therapy with imatinib mesylate, possibly an interferon-containing regimen or nonmyeloablative allogeneic transplantation may be considered.