Prognostic significance of Philadelphia chromosome-positive cells detected by the polymerase chain reaction after allogeneic bone marrow transplant for chronic myelogenous leukemia

Abstract

Although rare cells expressing the bcr/abl fusion transcript can be detected by the polymerase chain reaction (PCR) in patient blood or marrow after allogeneic bone marrow transplant (BMT) for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukemia (CML), the prognostic significance of this finding is unknown. This paper reports clinical, cytogenetic, and molecular data derived from 64 CML patients following allogeneic BMT. Nested primer PCR was performed on patient blood and bone marrow samples to detect the presence of residual bcr/abl (+) cells in CML patients considered to be in clinical remission at the time of study. Bcr/abl transcripts were detected in 37 of 64 patients for at least one timepoint post-BMT. Thirteen of these 37 bcr/abl (+) patients have subsequently relapsed, as defined by clinical and/or persistent cytogenetic findings, in contrast to 0 relapses among the 27 bcr/abl (-) patients (P = .0025). The median time from first (+) bcr/abl PCR signal to relapse was 150 days (range 90 to 832). Fifty-four patients were studied at two or more timepoints post- BMT: five of eight patients persistently bcr/abl (+) have relapsed; 5 of 23 patients with both bcr/abl (+) and (-) assays during follow-up have relapsed; and none of 23 patients persistently (-) have relapsed (cumulative actuarial relapse rates 77%, 20%, and 0%, respectively, P = .0017). These data indicate that among CML patients in apparent clinical remission after BMT, nested primer bcr/abl PCR can define subgroups with low, intermediate, and high risk of relapse. The pattern of bcr/abl PCR detection after transplant may aid in the development of trials designed to reduce the risk of relapse, or allow for early intervention in patients who fail to clear the malignant clone.