Early withdrawal immunosuppression improved mixed chimerism in hematopoietic stem cell transplantation for pediatric aplastic anemia
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Mixed chimerism (MC) occurs frequently with the risk of graft reject (GR) for aplastic anemia (AA) patients undergoing matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT). So far, no one knows how to adjust immunosuppression (IS) during MC. We retrospectively analyzed 87 consecutive pediatric patients. Early withdrawal (EW) IS and donor lymphocyte infusion (DLI) were attempted to reverse MC. The rate of MC was 26% (n = 23). Low dose cyclophosphamide (CY) (120–150 mg/kg) is an independent risk factor for MC (P = 0.0002) and increase dosage of Fludarabine (FLU) cannot eliminated it. Patients receiving 200 mg/kg CY had the lowest MC rate (8%) and best 3-year graft-versus-host disease (GVHD)/failure free survival (GFFS; 95%). Chimerism in T cells is more sensitive than that in whole blood (P = 0.001). In 17 patients with early-onset MC (ratio of DLI: 83% versus 82%), EW IS strategy is helpful to improving complete chimerism (CC) (63 vs. 295 days, P = 0.008). Our study shows that FLU is necessary to intensify CY + ATG conditioning to maintain the engraftment and 200 mg/kg CY + 150 mg/m2 FLU is recommended as a basic conditioning regimen. EW IS strategy should be considered as an important option to improve donor chimerism in early-onset MC.
