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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2232-2241. Prepublished online as a Blood First Edition Paper on July 10, 2008; DOI 10.1182/blood-2008-03-143636. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-143636v1 112/6/2232    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Davies, J. K. Articles by Guinan, E. C. Search for Related Content PubMed PubMed Citation Articles by Davies, J. K. Articles by Guinan, E. C. Related Collections Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies Jeff K. Davies1,2, John G. Gribben3, Lisa L. Brennan4, Dongin Yuk1, Lee M. Nadler1,2, and Eva C. Guinan4,5 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; 2 Department of Medicine, Brigham and Women's Hospital, Boston, MA; 3 Department of Medical Oncology, St Bartholomew's Hospital, London, United Kingdom; 4 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; and 5 Division of Hematology/Oncology, Children's Hospital, Boston, MA We report the outcomes of 24 patients with high-risk hematologic malignancies or bone marrow failure (BMF) who received haploidentical bone marrow transplantation (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by allostimulation in the presence of costimulatory blockade. Ninety-five percent of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T-cell dose of 29 x106/kg, only 5 of 21 evaluable patients developed grade C (n = 4) or D (n = 1) acute graft-versus-host disease (GVHD), with only one attributable death. Twelve patients died from treatment-related mortality (TRM). Patients reconstituted T-cell subsets and immunoglobulin levels rapidly with evidence of in vivo expansion of pathogen-specific T cells in the early posttransplantation period. Five patients reactivated cytomegalovirus (CMV), only one of whom required extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only 1 of 12 evaluable patients developed chronic GVHD. Eight patients survive disease-free with normal performance scores (median follow-up, 7 years). Thus, despite significant early TRM, ex vivo alloanergization can support administration of large numbers of haploidentical donor T cells, resulting in rapid immune reconstitution with very few viral infections. Surviving patients have excellent performance status and a low rate of chronic GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] J. K. Davies, L. M. Nadler, and E. C. Guinan Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation Science Translational Medicine, October 7, 2009; 1(1): 1ra3 - 1ra3. [Abstract] [Full Text] [PDF]

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