Introduction

Until recently, the progression to blast phase was considered inevitable for almost all patients with chronic myelogenous leukemia (CML).1 Except for a minority of patients able to tolerate interferon and achieve a complete cytogenetic response, or for those with an HLA-matched sibling and young enough to survive a bone marrow transplant, most patients entered the blastic phase of CML and died within 6 months to a year.2 Fortunately, advances in both transplantation and nontransplantation therapy have improved the outlook for patients with chronic-phase CML, and by extension, have changed the way in which patients entering the blast phase present and are approached therapeutically.

Imatinib mesylate, widely available by the year 2000, is currently the initial treatment of choice for the majority of patients with CML. Although follow-up is short, preliminary results have demonstrated that close to 80% are achieving complete remissions and less than 10% of the patients have progressed to blast phase by 4 years.3 Concurrently, the development of large marrow donor registries, coupled with improved transplantation techniques for older patients and for those undergoing unrelated donor transplants, have led to an increased use of transplantation for patients unresponsive to imatinib, who in the past would have been deemed ineligible for this procedure.4

Although the duration of response to imatinib is still unknown, and concerns over drug resistance have emerged, several situations seem probable: (1) a significant percentage of patients treated with imatinib will be long-term survivors and will not enter the blast phase; (2) patients entering the blast phase of disease will have already been treated with imatinib, which may influence their ability to respond to subsequent therapy; and (3) an increasingly higher percentage of chronic-phase CML patients will undergo hematopoietic stem cell transplantation at the development of clinical or laboratory evidence of imatinib failure with an expanding pool of "acceptable" donors. It is with this background we can examine the treatment options available to patients in the advanced phases of CML.

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