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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3308-3313.
Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-04-1614.
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TRANSPLANTATION
Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation
Steven Z. Pavletic,
Shelly L. Carter,
Nancy A. Kernan,
Jean Henslee-Downey,
Adam M. Mendizabal,
Esperanza Papadopoulos,
Roger Gingrich,
James Casper,
Saul Yanovich,
Daniel Weisdorf, for the members of the National Heart, Lung, and Blood Institute Unrelated Donor Marrow Transplantation Trial
From the University of Nebraska Medical Center, Omaha; The EMMES Corporation, Rockville, MD; Memorial Sloan-Kettering Cancer Center, New York, NY; University of South Carolina, Columbia; University of Iowa, Iowa City; Medical College of Wisconsin, Milwaukee; Medical College of Virginia, Richmond; University of Minnesota, Minneapolis.
Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P = .27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P = .29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P = .27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD.
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