title: 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.
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) > or =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 <0.01). All eight patients with MC in peripheral blood > or =1 month after SCT relapsed 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 vs morphological 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.
authors.affiliation: Center for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Mattsson
authors.forename: M
authors.initials: M
authors.lastname: Uzunel
authors.forename: L
authors.initials: L
authors.lastname: Tammik
authors.forename: J
authors.initials: J
authors.lastname: Aschan
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D019070:Cell Lineage; D002469:Cell Separation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000592:standards*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D011237:Predictive Value of Tests; D012008:Recurrence; D012680:Sensitivity and Specificity; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000592:standards