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 Journal Article


Authors: Wagner, J. E.; Thompson, J. S.; Carter, S. L.; Kernan, N. A.
Article Title: 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
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.
Keywords: adolescent; adult; controlled study; treatment outcome; disease-free survival; middle aged; leukemia; survival rate; major clinical study; clinical trial; methotrexate; t-lymphocytes; controlled clinical trial; phase 2 clinical trial; randomized controlled trial; recurrence; allogenic bone marrow transplantation; chronic myeloid leukemia; confidence interval; hospitalization; donor; statistical significance; neutrophil; graft versus host reaction; t cell depletion; immunosuppressive treatment; cyclosporin a; bone marrow transplantation; leukemia relapse; graft vs host disease; cytomegalovirus infection; cyclosporine; immunosuppressive agents; lymphocyte depletion; hematologic diseases; recipient
Journal Title: Lancet
Volume: 366
Issue: 9487
ISSN: 0140-6736
Publisher: Elsevier Science, Inc.  
Date Published: 2005-08-27
Start Page: 733
End Page: 741
Language: English
DOI: 10.1016/s0140-6736(05)66996-6
PUBMED: 16125590
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 79" - "Export Date: 24 October 2012" - "CODEN: LANCA" - "Source: Scopus"
Altmetric
Citation Impact
MSK Authors
  1. Nancy Kernan
    477 Kernan