Abstract • 152

Peripheral mobilized HLA-mismatched haploidentical CD34+ progenitors were isolated and used for the hematopoietic reconstitution after myeloablative therapy in 27 pediatric patients with various diseases (ALL 11, AML 4, MDS 4, CML 2, NHL 1, immunodeficiency 3, osteopetrosis 1, SAA 1). Fifteen donors were HLA three-loci mismatch, 7 donors were two-loci and 5 donors were one-locus mismatch. 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 18.2 × 106/kg (range 5.4 - 39 × 106/kg) and the average number of infused T-lymphocytes was 1.6 × 104/kg. The time to reach >1000/µl neutrophiles and independence from platelet substitution was 11 and 27 days, respectively. Due to the low T cell number, only a short term (4 pts) or no prophylaxis (23 pts) for graft-versus-host disease (GvHD) even in the three-loci mismatch situation was necessary. A significant GvHD was only seen in 2 patients after add-back of donor T-lymphocytes, which was performed in 15 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 EBV-associated lymphoproliferative syndrome was observed. A primary engraftment was seen in 22 patients. Rejection occured in 5 patients. In four of these 5 patients, however, a second transplant using purified CD34+ cells from the same donor after an immunological reconditioning regimen (steroids and anti-CD3 antibody) resulted in a complete and sustained hematopoietic reconstitution. Fifteen of the 27 patients are alive and 13 are disease-free with a median follow-up of 14 months (range 4-37). The main cause of death was relapse (7 patients), only 1 fatal infection was seen. Our data suggest that the transplantation of megadoses of isolated haploidentical CD34+ cells is a realistic therapeutic option for patients who have otherwise no suitable donor.