title: Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children.
abstract: We performed HLA-mismatched stem cell transplantation with megadoses of purified positively selected mobilized peripheral blood CD34(+) progenitor cells (PBPC) from related adult donors in 39 children lacking an otherwise suitable donor. The patients received a mean number of 20.7 +/- 9.8 x 10(6)/kg purified CD34(+) and a mean number of 15.5 +/- 20.4 x 10(3)/kg CD3(+) T lymphocytes. The first seven patients received short term (<4 weeks) GVHD prophylaxis with cyclosporin A, whereas in all the following 32 patients no GVHD prophylaxis was used. In 38 evaluable patients, five patients experienced primary acute GVHD grade I and one patient grade II. In 32 patients, no signs of primary GVHD were seen and GVHD only occurred after T cell add backs. T cell reconstitution was more rapid if the number of transplanted CD34(+) cells exceeded 20 x 10(6)/kg. Of the 39 patients, 15 are alive and well, 13 died due to relapse and 10 transplant-related deaths occurred. We conclude that the HLA barrier can be overcome by transplantation of megadoses of highly purified mismatched CD34(+) stem cells. GVHD can be prevented without pharmacological immunosuppression by the efficient T cell depletion associated with the CD34(+) positive selection procedure. This approach offers a promising therapeutic option for every child without an otherwise suitable donor.
authors.affiliation: Department of Pediatric Hematology/Oncology and Blood Bank, University of Tübingen, Tübingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Schumm
authors.forename: S
authors.initials: S
authors.lastname: Neu
authors.forename: A
authors.initials: A
authors.lastname: Geiselhart
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: P G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: J
authors.initials: J
authors.lastname: Greil
authors.forename: D
authors.initials: D
authors.lastname: Stachel
authors.forename: R J
authors.initials: RJ
authors.lastname: Herzog
authors.forename: D
authors.initials: D
authors.lastname: Niethammer
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34 / Q000097:blood*; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D010290:Parents; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34