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.
