Treatment of High-Risk Acute Leukemia with T-Cell–Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype

作者：Franco Aversa, Antonio Tabilio, Andrea Velardi, Isabel B. Cunningham, Adelmo Terenzi, Franca Falzetti, Loredana Ruggeri, Giuliana Barbabietola, Cynthia Aristei, Paolo Latini, Yaīr Reisner, Massimo F. Martelli, Rita Felicini, Flavio Falcinelli, Alessandra Carotti, Katia Perruccio, Stelvio Ballanti, Antonella Santucci, Cesare Gambelunghe · 发表于：New England Journal of Medicine · 年份：1998 · DOI：10.1056/nejm199810223391702 · 被引用次数：1180 · 研究领域：Hematopoietic Stem Cell Transplantation、Mesenchymal stem cell research、Acute Myeloid Leukemia Research

BACKGROUND: In this study we tried to achieve successful transplantation in patients with acute leukemia with the use of hematopoietic stem cells from donors who shared only one HLA haplotype with the recipient (a "full-haplotype mismatch"). To prevent graft failure, large doses of T-cell-depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient. METHODS: Forty-three patients with high-risk acute leukemia who were scheduled for transplantation received total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. The graft consisted of peripheral-blood progenitor cells that had been mobilized in the donor with recombinant granulocyte colony-stimulating factor and also, in 28 cases, bone marrow. Bone marrow from the donor was depleted of T lymphocytes by processing with soybean agglutinin and E-rosetting. T-cell depletion of peripheral-blood mononuclear cells was achieved by E-rosetting followed by positive selection of CD34+ cells. No post-transplantation prophylaxis against graft-versus-host disease (GVHD) was administered. RESULTS: In all the patients, full donor-type engraftment was achieved. In none of the patients who could be evaluated did acute or chronic GVHD develop. Regimen-related toxicity was minimal. Eleven of the 23 patients with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with acute myeloid leukemia. Transplantation-r...