Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): A multi-centre, randomised phase II-III trial

John E. Wagner, John S. Thompson, Shelly L. Carter, Nancy A. Kernan

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

Abstract

Background: Graft-versus-host disease (GVHD) reduces the efficacy of unrelated donor bone marrow transplantation in patients with lymphohaemopoietic malignancy. A multi-centre, randomised trial was undertaken to determine the effects of ex-vivo T-cell depletion versus methotrexate and cyclosporine immunosuppression on 3-year disease-free survival. Methods: Between Mar 1, 1995, and Oct 31, 2000, 405 patients with lymphohaemopoietic malignancy, from 15 participating centres, were randomly assigned to undergo transplantation with either T-cell depleted marrow and cyclosporine A (TCD arm; n=201) or methotrexate and cyclosporine A after transplantation of T-replete marrow (M/C arm; n=204). The primary outcome was 3-year disease-free survival and was analysed by intention to treat. Findings: Five patients died before transplantation. Seven in the TCD arm received T-replete grafts. Disease-free survival at 3 years was 27% (95% CI 21-33) and 34% (27-40) in recipients of TCD and M/C, respectively (p=0·16). TCD was associated with significantly more rapid neutrophil recovery (15 days vs 20 days, p<0·0001), less grade III-IV acute GVHD (18% vs 37%, p<0·0001), reduced grade III-IV toxicities (19% vs 29%, p=0·017), reduced duration of initial hospitalisation, but higher risk of chronic myelogenous leukaemia relapse (20% vs 7%, p=0·009) and cytomegalovirus infection (28% vs 17%, p=0·023) than was M/C. Interpretation: Disease-free survival at 3 years did not differ between TCD and M/C groups. Relapse and opportunistic infection are important obstacles to successful unrelated donor bone marrow transplantation, irrespective of the method of GVHD prophylaxis used.

Original languageEnglish (US)
Pages (from-to)733-741
Number of pages9
JournalLancet
Volume366
Issue number9487
DOIs
StatePublished - Aug 27 2005

Bibliographical note

Funding Information:
We thank the many clinical investigators who have advanced the field; the many physicians and nurses who have diligently cared for these patients; the many search coordinators and the dedicated staff of the National Marrow Donor Program for their work; and Angela Norman for her assistance in the preparation of this manuscript. This trial was supported by a contract from the National Heart, Lung and Blood Institute (N01-HB-47095 [JEW], N01-HB-47097 [JST], N01-HB-47094 [SLC] and N01-HB-47098 [NAK]).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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