Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients

Abstract

Graft failure is a life-threatening complication after transplantation of hematopoietic stem cells. We report a cohort of 11 pediatric patients with leukemias ( n = 8) and severe aplastic anemia ( n = 3) who experienced graft rejection after myeloablative transplantation from mismatched related donors ( n = 6) or after cord blood or matched unrelated donor transplantation ( n = 5). In the latter, the original donor was not available anymore. All patients were re-transplanted with CD34 + selected or CD3/CD19 depleted stem cells from a second, haploidentical donor. Median time span from diagnosis of rejection to second transplant was 9 days. Reconditioning regimens comprised total lymphoid irradiation, thiotepa, fludarabine, ATG/OKT3 and were well tolerated. A median number of 23.5 × 10 6/kg stem cells with 95,000/kg residual T-cells were infused. Sustained engraftment of neutrophiles/platelets and complete donor chimerism was achieved in all patients (ANC > 500/μl: 9 (11–32) days). No GvHD > grade II was observed. 8/11 patients are disease free (median follow up 1.9 years; 1 year-EFS = 72%). Causes of death were: pneumonitis, infection, relapse. Thus, haploidentical transplantation represents a realistic option to rescue patients with graft failure within a short time span, for whom a second donation from the original donor is not available. The use of different donors may contribute to avoid a second rejection.