Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation

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Abstract
One of the major complications after allogeneic stem cell transplantation (SCT) in patients with malignant disease is a high frequency of relapse. We have prospectively analyzed the clinical impact of recipient-derived chimeric cells in 30 patients with acute myeloid leukemia and myelodysplastic syndrome after SCT. In order to improve sensitivity and specificity, all samples were cell-separated by using immunomagnetic beads according to the patient's leukemia phenotype, expressed at diagnosis or relapse before SCT. Twelve out of 30 patients experienced a clinical relapse after SCT. Median follow-up time for patients alive and without relapse (n = 15) was 30 (16–47) months. Mixed chimerism in peripheral blood (PB) and bone marrow (BM) ⩾1 month post SCT, in the leukemia-affected cell lineage, was detected in 14/30 patients. Ten of these 14 patients relapsed as compared to 2/16 with donor chimerism (DC) (P vs 4/22 DC patients (P < 0.001). MC was detected a median of 66 (23–332) days before hematological relapse. No correlation was found between T cell MC and relapse. In this study, chimerism analysis showed a higher sensitivity and specificity vsmorphological examination. In conclusion, this study may provide a rational basis for treatment with adoptive immunotherapy at an earlier time after SCT than at present, in patients with AML and MDS, in order to treat recurrences of malignant disease.

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