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

The bcr-abi chimeric messenger RNA is frequently detected in chronic myelol d leukemia (CML) patients after bone marrow transplantation, It was previou sly reported that the relapse risk of bcr-abl detection 6 to 12 months afte r transplantation was greater than 40%. This risk decreased as the time bet ween transplantation and detection increased. To further define the relapse risk associated with bcr-abi molecular detection in "late" CML survivors, 379 consecutive CML patients alive at 18 months after transplantation or la ter were studied. Ninety of 379 patients (24%) had at least one positive bc r-abl test 18 months after transplantation or later; 13 of 90 bcr-abi-posit ive patients (14%) and 3 of 289 bcr-abi-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 with bcr-abl detection w as 19.2 (P < .0001). The stage of disease, chronic graft-versus-host diseas e, and the donor type did not alter the association between bcr-abl and rel apse. Quantification of bcr-abl was performed on 344 samples from 85 bcr-ab i-positive patients by means of a real-time quantitative reverse transcript ase-polymerase chain reaction assay. The median bcr-abi change of patients who relapsed was significantly greater than those that remained in remissio n (P = .002). The median bcr-abl level at relapse was 40 443 bcr-abi copies per jig RNA (range, 960-299 552). Of 73 bcr-abi-positive patients who fail ed to relapse, 69% had only one positive test at a median of 24 copies bcr- abl per mug RNA. The detection of bcr-abl is common following transplantati on. The prognostic significance of a qualitative bcr-abi can be refined by quantitative assays and thus may target patients who would benefit from ear ly intervention. (C) 2001 by The American Society of Hematology.