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 pur ified positively selected mobilized peripheral blood CD34(+) progenitor cel ls (PBPC) from related adult donors in 39 children lacking an otherwise sui table 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 ly mphocytes. The first seven patients received short term (<4 weeks) GVHD pro phylaxis with cyclosporin A, whereas in all the following 32 patients no GV HD prophylaxis was used. In 38 evaluable patients, five patients experience d primary acute GVHD grade I and one patient grade II. In 32 patients, no s igns of primary GVHD were seen and GVHD only occurred after T cell add back s. 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 concl ude that the HLA barrier can be overcome by transplantation of megadoses of highly purified mismatched CD34(+) stem cells. GVHD can be prevented witho ut pharmacological immunosuppression by the efficient T cell depletion asso ciated with the CD34(+) positive selection procedure. This approach offers a promising therapeutic option for every child without an otherwise suitabl e donor.