Impact of Prior Therapy with Imatinib Mesylate on the Outcome of Hematopoietic Cell Transplantation (HCT) for Chronic Myeloiod Leukemia (CML).

Abstract

Imatinib mesylate (IM, Gleevec®) has largely supplanted allogeneic HCT as first line therapy for CML. Nevertheless, many persons with CML eventually undergo HCT raising the question of whether prior IM-therapy impacts HCT outcome. The effect of IM on HCT outcomes is unknown. Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 409 subjects treated with IM pretransplant (IM+) and 900 subjects who did not (IM-), we evaluated transplant-related mortality (TRM), acute graft-vs.-host disease (GVHD), leukemia relapse (defined as hematologic), leukemia-free survival (LFS) and survival. Transplants occurred from 1999–2003. Only data from centers that reported data on at least 80% of IM+ subjects which also concurrently treated IM- subjects were included to minimize potential bias. Because of population differences, results are presented separately for 1st chronic phase (CP1) and all other phases (> CP1). In both groups, IM+ subjects were transplanted more recently, had a longer interval from diagnosis to transplant, were more likely to receive peripheral blood than bone marrow, and to have unrelated donors. Within the CP1 group, 52% had planned to undergo transplant regardless of response to IM, while transplant was prompted by IM failure or no response in 37% and by IM intolerance in 9%. 52% of CP1 subjects received IM within a month of transplant. In CP1 subjects, IM-therapy prior to HCT was associated with better survival. Other significant factors associated with better survival in CP1 patients were better matched donor (p<0.0001), use of bone marrow (RR 0.66; p=0.002), and transplants < 1 year from diagnosis (RR 0.68; p=0.002). There was also a trend towards less TRM and more relapses; LFS was similar. Because of concern about possible selection biases, a matched-pairs analysis considering interval from diagnosis to HCT (+/− 3 mos), HLA-match, graft-type and sex-match was performed with 143 IM+ CP1 subjects and 236 IM- controls. Results confirmed a higher survival rate and less TRM in IM+ subjects. In subjects > CP1, use of IM before HCT was not associated with TRM, relapse, LFS or survival. Acute GVHD rates were similar between IM+ and IM- subjects regardless of leukemia phase.In summary, treatment with IM before HCT while in CP1 is associated with higher survival and trends towards less TRM and more hematologic relapses after transplant. In subjects > CP1, prior treatment with IM was associated with similar outcomes seen in patients not receiving IM before HCT. These results should be reassuring to patients receiving IM or CP1 patients contemplating a trial of IM before HCT.StageOutcomeRR95% CIp-valueCP1Survival0.630.46–0.880.006LFS0.890.68–1.150.36TRM0.700.49–0.980.04Hematologic Relapse1.541.02–2.350.04Beyond CP1Survival0.930.74–1.180.57LFS1.050.84–1.320.67TRM0.870.64–1.180.35Hematologic Relapse1.350.95–1.890.09