The emergence of Ph−, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate

Objective. To describe clinical and laboratory features of a cohort of patients with chronic myelogenous leukemia (CML) who developed Ph−, trisomy 8+ metaphases while on treatment with imatinib mesylate. Patients and Methods. Conventional cytogenetics and triple-color interphase fluorescence in situ hybridization were used to identify 5 of 310 studied patients who, on follow-up analysis, had Ph−, trisomy 8+ cells while on therapy. Results. None of the 5 patients had cytogenetic evidence of clonal evolution at the start of treatment with imatinib. All patients developed grade 3 or 4 neutropenia and thrombocytopenia during treatment. The emergence of Ph−, trisomy 8+ metaphases was seen at 3, 6, 13, 16, and 18 months from the start of treatment and was present at multiple time points. The maximum number of trisomy 8 metaphases ranged from 25 to 50%. Concomitantly, all patients had a profound suppression of Ph+ cells (ranging from 0 to 65%) as well as the appearance of normal metaphases, ranging from 6 to 55%. None of the patients has shown clinical or hematologic signs of progression to a more advanced phase of CML. Conclusions. While on treatment with imatinib mesylate a small group (less than 5%) of patients with CML developed Ph− trisomy 8+ clone associated with pancytopenia. None of the patients developed clinical or hematological signs of progression to a more advanced phase of CML. These observations suggest that identification of trisomy 8 cells may represent clonal Ph− cells that were uncovered by treatment with a selective and potent inhibitor of Ph+ cells.