Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats

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Abstract
In this study, we analysed the chimaeric status of peripheral blood leucocytes (PBLs) in recipients of allogeneic bone marrow transplantation (BMT) with the use of short tandem repeat (STR) microsatellite markers for monitoring the efficacy of BMT and donor leucocyte infusions (DLIs). A set of four STR markers was used with a highly discrimative capacity between individuals. STRs were detected by polymerase chain reaction (PCR) and were analysed by gene scanning (STR‐GS). Between June 1990 and December 1998, 52 patients treated with BMT for chronic myeloid leukaemia (CML) were analysed. Seventeen patients relapsed after BMT and two patients never achieved remission after BMT. Fourteen of the 17 patients achieved a complete donor chimaerism after BMT, as detected by the presence of only donor STR‐GS fragments, and in three cases a weak recipient STR‐GS signal remained persistently detectable after BMT. A reappearance or increase of recipient STR‐GS signals was indicative of relapse, which was mostly detected by STR‐GS several months before relapse was diagnosed clinically. Nineteen patients were treated with DLI for reappearance of CML after BMT which resulted in complete remission in 17 patients, concordant with the disappearance of recipient STR‐GS signals. More importantly, DLI treatment could be guided based upon the STR‐GS data, which prevented unnecessary extra DLI courses that could cause toxicity. This study indicates that STR‐GS is an effective and reliable method for monitoring BMT recipients.

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