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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1701-1707

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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

Jerald P. Radich, Ted Gooley, Eileen Bryant, Tom Chauncey, Reginald Clift, Lan Beppu, Scott Edmands, Mary E. D. Flowers, Keith Kerkof, Ross Nelson, and Frederick R. Appelbaum

From the Clinical Research Division of the Fred Hutchinson Cancer Research Center, the University of Washington School of Medicine, and the Veteran's Affairs Medical Center, Seattle, WA.

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-abl test 18 months after transplantation or later; 13 of 90 bcr-abl-positive patients (14%) and 3 of 289 bcr-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 with bcr-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-abl and 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 copies bcr-abl per µg RNA. The detection of bcr-abl is 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.

© 2001 by The American Society of Hematology.
 

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