Transplantation of megadoses of purified haploidentical stem cells.
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 x 10(6)/kg (range 5.4-3.9 x 10(6)/kg) and the average number of infused T-lymphocytes was 1.4 x 10(4)/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 x 10(6)/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.
Handgretinger
R
R
Children's University Hospital, University of Tübingen, Germany.
Schumm
M
M
Lang
P
P
Greil
J
J
Reiter
A
A
Bader
P
P
Niethammer
D
D
Klingebiel
T
T
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy; D007223:Infant; D007938:Leukemia / Q000628:therapy; D016131:Lymphocyte Subsets / Q000276:immunology*; D009190:Myelodysplastic Syndromes / Q000628:therapy; D010022:Osteopetrosis / Q000628:therapy
D018952:Antigens, CD34; D015415:Biomarkers