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

Lancet. 2005;366(9487):733-41. doi: 10.1016/S0140-6736(05)66996-6.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation* / adverse effects
  • Bone Marrow Transplantation* / immunology
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Diseases / mortality
  • Hematologic Diseases / therapy*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Leukemia / mortality
  • Leukemia / therapy*
  • Lymphocyte Depletion
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Middle Aged
  • Recurrence
  • Survival Rate
  • T-Lymphocytes


  • Immunosuppressive Agents
  • Cyclosporine
  • Methotrexate