The significance of bcr-abl molecular detection in chronic myeloid leukemia patients “late,” 18 months or more after transplantation

Abstract

Abstract The bcr-abl chimeric messenger RNA is frequently detected in chronic myeloid leukemia (CML) patients after bone marrow transplantation. It was previously reported that the relapse risk of bcr-abl detection 6 to 12 months after transplantation was greater than 40%. This risk decreased as the time between transplantation and detection increased. To further define the relapse risk associated with bcr-abl molecular detection in “late” CML survivors, 379 consecutive CML patients alive at 18 months after transplantation or later were studied. Ninety of 379 patients (24%) had at least one positive bcr-abltest 18 months after transplantation or later; 13 of 90bcr-abl–positive patients (14%) and 3 of 289bcr-abl–negative patients (1.0%) relapsed. The median time from bcr-abl detection to relapse was 916 days (range, 251-2654 days). The hazard ratio of relapse associated withbcr-abl detection was 19.2 (P < .0001). The stage of disease, chronic graft-versus-host disease, and the donor type did not alter the association between bcr-abland relapse. Quantification of bcr-abl was performed on 344 samples from 85 bcr-abl–positive patients by means of a real-time quantitative reverse transcriptase–polymerase chain reaction assay. The median bcr-abl change of patients who relapsed was significantly greater than those that remained in remission (P = .002). The median bcr-abl level at relapse was 40 443 bcr-abl copies per μg RNA (range, 960-299 552). Of 73 bcr-abl–positive patients who failed to relapse, 69% had only one positive test at a median of 24 copiesbcr-abl per μg RNA. The detection of bcr-ablis common following transplantation. The prognostic significance of a qualitative bcr-abl can be refined by quantitative assays and thus may target patients who would benefit from early intervention.