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 ch ronic myeloid leukemia (CML) for the presence of the bcr-abl transcrip t detected by the polymerase chain reaction (PCR) to understand the fr equency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 an d 192 months after BMT. A positive PCR test at 3 months post-BMI was n ot statistically significantly associated with an increased risk of re lapse compared with PCR-negative patients. However, a positive PCR ass ay at 6 months and beyond was highly associated with subsequent relaps e. The Kaplan-Meier estimate of relapse for patients testing PCR-posit ive 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 resu lt at 6 to 12 months post-BMT, the type of BMT donor (allogeneic match ed donor v mismatched or unrelated), and the prescence of acute GVHD w ere 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 outcom e 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 on ly one patient relapsed, There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses sh ow that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provi des an opportunity for early therapeutic intervention. (C) 1995 by The American Society of Hematology.