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Allografting

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 × 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.

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Acknowledgements

We gratefully acknowledge the cooperation with following colleagues who took clinical care of one patient each and provided follow-up data: Ewa Koscielnak, MD (Olgahospital Stuttgart, Germany), Christina Peters, MD (St Anna Kinderspital, Vienna, Austria), Wolfgang Schwinger, MD (University of Graz, Austria), Alfred Reiter, MD (Medical School Hannover, Germany) and Stefan Müller-Weihrich, MD (Technical University, München, Germany). The authors are grateful to A Babarin-Dorner, C Faleyras, U Krautter, and R Siedner for excellent technical assistance. We thank Prof Dr Lothar Kanz for critical reading of the manuscript and for helpful suggestions and Margarete Ruck for helping prepare the manuscript. This work was supported by the German Jose Carreras Leukemia Foundation.

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Handgretinger, R., Klingebiel, T., Lang, P. et al. Megadose transplantation of purified peripheral blood CD34+progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 27, 777–783 (2001). https://doi.org/10.1038/sj.bmt.1702996

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