Department of Pediatric Hematology/Oncology and Blood Bank, University of Tübingen, Tübingen; von Haunersches Kinderspital, München; and Children's University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany

Correspondence to: Dr Niethammer, Children's University Hospital, Hoppe-Seyler-Str 1, 72076 Tübingen, Germany

^aThe first two authors contributed equally to this paper

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 ´ 10⁶/kg purified CD34⁺ and a mean number of 15.5 ± 20.4 ´ 10³/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 ´ 10⁶/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. Bone Marrow Transplantation (2001) 27, 777-783.

mismatch transplantation; CD34-positive selection; donor lymphocyte infusion