Transplantation of Megadoses of Purified Haploidentical Stem Cells

Abstract: Peripheral mobilized parental CD34+ progenitors were isolated and used for the hematopoietic reconstitution after a myeloablative therapy in 23 pediatric patients with various diseases. Fourteen donors were human leukocyte antigen (HLA) three‐loci mismatches, 6 donors were two‐loci and 3 donors were one‐locus mismatches. For depletion of T‐lymphocytes, a positive selection of the mobilized peripheral CD34+ progenitors using the method of magnetic‐activated cell sorting (MACS) was used. The purity of the CD34+ cells after MACS‐sorting was 98‐99%, the average number of transplanted CD34+ cells was 14.2 3 × 106/kg (range 5.4‐3 9 × 3 I 06/kg) and the average number of infused T‐lymphocytes was 1.4 × 3 104/kg. Due to this low T cell number, only a short‐term or no prophylaxis of graft‐versus‐host disease (GVHD) was necessary and no GVHD was seen. A significant GVHD was only seen in patients after add‐back of donor T‐lymphocytes, which was performed in some patients for prevention of relapse or in patients who showed a transient mixed chimerism. Since the B lymphocyte contamination of the isolated CD34+ cells was low in the range of 0.2%, no Epstein‐Barr virus (EBV)‐associated lymphoproliferative syndrome was observed. A primary engraftment was seen in 18 patients. Nonengraftment and rejection occurred in three and two patients, respectively. In four of these 5 patients, a second transplant using purified CD34+ cells from the same donor after an immunological reconditioning regimen resulted in a complete and sustained hematopoietic reconstitution. The speed of the immunological recovery was dependent on the number of transplanted CD34+ cells and was more rapid if this number was >20 × 3 106/kg. Eleven of the 23 patients are alive and disease free with a median follow‐up of 12 months (range 2‐30). The main cause of death was relapse (7 patients), and only one fatal infection was seen. Our data suggest that the transplantation of megadoses of haploidentical CD34+ cells is a realistic therapeutic option for patients who otherwise have no suitable donor, and an alternative to the use of unrelated cord blood.

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