Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children.
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.
Handgretinger
R
R
Department of Pediatric Hematology/Oncology and Blood Bank, University of Tübingen, Tübingen, Germany.
Klingebiel
T
T
Lang
P
P
Schumm
M
M
Neu
S
S
Geiselhart
A
A
Bader
P
P
Schlegel
P G
PG
Greil
J
J
Stachel
D
D
Herzog
R J
RJ
Niethammer
D
D
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
D018952:Antigens, CD34