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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Minnesota Blood and Marrow Transplantation Program, Minneapolis, MN 55455, USA. wagne002@umn.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: John S
authors.initials: JS
authors.lastname: Thompson
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006402:Hematologic Diseases / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D013601:T-Lymphocytes
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate