Cytogenetic studies in patients on imatinib

Abstract

With the introduction of imatinib (Gleevec) (formerly STI571) for the treatment of chronic myeloid leukemia (CML), the various diagnostic methods used to monitor patients must be re-evaluated. Conventional cytogenetics has been the established method for follow-up of patients treated with interferon-alpha (IFN-alpha), and the prognostic value of major and complete cytogenetic remission was demonstrated in a number of studies. In patients on imatinib, these endpoints will likely remain valid, although longer observation is required. Cytogenetic remission as a time-dependent variable may aid risk stratification early on. Clonal evolution, ie, the presence of cytogenetic abnormalities in addition to the Philadelphia (Ph) chromosome, may provide important prognostic information as to the likely response to imatinib in all phases of CML but must be interpreted within the context of other disease characteristics. In some patients, clonal evolution is related to imatinib resistance. Information regarding the impact of specific types of additional cytogenetic abnormalities is still limited. Surprisingly, nonrandom karyotypic abnormalities have also been noted in the Ph-negative cells of some patients in cytogenetic remission. This is a novel phenomenon whose causality and prognostic implications require thorough and systematic evaluation.