Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract

We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph- ) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL.