DETECTION OF BCR-ABL TRANSCRIPTS IN PHILADELPHIA-CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA AFTER MARROW TRANSPLANTATION

Thirty-six patients with Philadelphia chromosome-positive acute lympho blastic leukemia (Ph(+) ALL) were studied for the presence of the bcr- abl fusion mRNA transcript after an allogeneic matched related (N = 12 ), partially matched related (N = 4), matched unrelated (N = 14), auto logous (N = 5), or syngeneic (N = 1) bone marrow transplant (BMT). Sev enteen were transplanted in relapse, and 19 were transplanted in remis sion. Twenty-three patients had at least one positive bcr-abl polymera se chain reaction (PCR) assay after BMT either before a relapse or wit hout subsequent relapse. Ten of these 23 relapsed after a positive ass ay at a median time from first positive PCR assay of 94 days (range, 2 8 to 416 days). By comparison, only 2 relapses occurred in the 13 pati ents with no prior positive PCR assays; both patients had missed at le ast one scheduled follow-up assay and were not tested 2 months and 26 months before their relapse. The unadjusted relative risk (RR) of rela pse associated with a positive PCR assay compared with a negative assa y was 5.7 (95% confidence interval 1.2 to 26.0, P = .025). In addition , the data suggest that the type of bcr-abl chimeric mRNA detected pos ttransplant was associated with the risk of relapse: 7 of 10 patients expressing the p190 bcr-abl relapsed, compared with 1 of 8 who express ed only the p210 bcr-abl mRNA (P = .02, log-rank test). The RR of p190 bcr-abl positivity compared to PCR-negative patients was 11.2 (confid ence interval 2.3-54.8, P = 0.003), whereas a positive test for p210 b cr-abl was apparently not associated with an increased relative risk. In separate multivariable models, PCR positivity remained a statistica lly significant risk factor for relapse after separately adjusting for donor (unrelated and partially matched v matched, autologous, and syn geneic), remission status at the time of transplant, the presence of a cute graft-versus-host disease (GVHD), and type of conditioning regime n (total body irradiation dose of less than or equal to 1,200 cGy v >1 ,200 cGy). The PCR assay appears to be a useful test for predicting pa tients at high risk of relapse after BMT and may identify patients who might benefit from therapeutic interventions. The finding that the ex pression of p190 bcr-abl may portend an especially high risk of relaps e suggests a different clinical and biologic behavior between p190 and p210 bcr-abl. (C) 1997 by The American Society of Hematology.