Mismatched T cell-depleted hematopoietic stem cell transplantation for children with high-risk acute leukemia

The aim of this study was to extend allogeneic hematopoietic stem cell tran splantation to leukemia patients without a matched donor. To prevent graft failure, large doses of T cell-depleted hematopoietic stem cells were trans planted following a highly myeloablative and immunosuppressive conditioning regimen. Fifteen children with high-risk acute leukemia received T cell-de pleted hematopoietic stem cells from full-haplotype mismatched family membe rs after a conditioning regimen that included single-dose TBI, thiotepa, AT G and fludarabine. To prevent GVHD, marrow cells were T-depleted by soybean agglutinin and E-rosetting, peripheral blood cells by E-rosetting followed by positive selection of the CD34(+) cells, No post-transplant prophylaxis for GVHD was administered. In all patients full donor-type engraftment was achieved, None of the evaluable patients developed either acute or chronic GVHD. Regimen-related toxicity was minimal. Five patients are alive and ev ent-free at a median follow-up of 18 months (range 13-28), All surviving pa tients have a good quality of life. Seven patients have relapsed. This stud y shows that GVHD and graft failure, which limited the use of full-haplotyp e mismatched bone marrow transplants, have been overcome. Since almost all children have a mismatched relative, advances in this area should make mism atched transplants a routine consideration for patients with high-risk leuk emia without a matched related or unrelated donor.