Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients.
We studied 346 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the polymerase chain reaction (PCR) to understand the frequency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3 months post-BMT was not statistically significantly associated with an increased risk of relapse compared with PCR-negative patients. However, a positive PCR assay at 6 months and beyond was highly associated with subsequent relapse. The Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12 months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier estimate of survival at 4 years for the PCR-positive patients was 74% compared with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated that a PCR-positive result at 6 to 12 months post-BMT, the type of BMT donor (allogeneic matched donor v mismatched or unrelated), and the presence of acute GVHD were independent risk factors for subsequent relapse. The relative risk (RR) for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95% confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients (> 36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%) tested positive for bcr-abl, but only one patient relapsed. There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provides an opportunity for early therapeutic intervention.
Radich
J P
JP
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Gehly
G
G
Gooley
T
T
Bryant
E
E
Clift
R A
RA
Collins
S
S
Edmands
S
S
Kirk
J
J
Lee
A
A
Kessler
P
P
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D012306:Risk; D016037:Single-Blind Method; D014158:Transcription, Genetic; D016896:Treatment Outcome
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl