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

Lang P, Mueller I, Greil J, Bader P, Schumm M, Pfeiffer M, Hoelle W, Klingebiel T, Heinzelmann F, Belka C, Schlegel PG, Kremens B, Woessmann W, Handgretinger R

Department of Pediatric Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Hoppe Seyler Straße 1, 72076 Tübingen, Germany.

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 23.5x10(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/mul: 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.

Published 10 December 2007 in Blood Cells Mol Dis, 40(1): 33-39.
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