Objective: To investigate the value of sequential and quantitative analysis of donor chimerism (DC) to predict the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), to determine the optimal time point of adoptive immunotherapy and to estimate the efficacy of adoptive immunotherapy.
Methods: Quantitative analysis of DC was performed with multiplex PCR amplification of short tandem repeats markers (STR-PCR) and capillary electrophoresis with fluorescence detection in 84 patients who received allo-HSCT. Sequential chimerism both prior to and following adoptive immunotherapy were evaluated in 16 patients.
Results: Increase of mixed chimerism and decrease of DC < 90% were found in 22 of the 84 patients. Six of the 22 patients who did not receive donor lymphocyte infusion (DLI) all died of relapse. Adoptive immunotherapy was used to treat the remaining 16 patients. Before the time of relapse or graft rejection, STR-PCR indicated decrease of DC in 12 of the 16 patients, with levels ranging from 24.8% - 86.2%. A response to immunotherapy was achieved in 11 of the 16 patients (68.8%). In these patients, the value of DC increased with conversion to a predominant donor profile (> or =90%). 6 of the 11 patients converted to stable full donor chimerism (FDC) and 5 of the 11 patients to transformed stable mixed chimerism (MC) shortly after immunotherapy. All these 11 patients who responded to immunotherapy developed graft versus host disease (GVHD). While in the patient without response, the level of DC decreased persistently or declined after a transient increase. Three patients without response received second DLI but still failed to response.
Conclusion: The results demonstrate that sequential and quantitative monitoring of DC can identify the patients who have high risk of relapse or graft failure and can be used to guide adoptive immunotherapy at early stage to improve the response of immunotherapy in those patients who undergo cytogenetic or molecular relapse. Furthermore the serial and quantitative detection of DC has been shown to be a valuable tool to evaluate early the efficacy of treatment. As well, it can present a rational basis for treatment intensification in patients who did not respond to first-line adoptive immunotherapy treatment.