Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial.
Abstract | BACKGROUND: METHODS: Between May 26, 2003, and Feb 8, 2007, 202 patients with haematological malignancies were centrally randomly assigned using computer-generated centre-stratified block randomisation between treatment groups receiving ciclosporin and methotrexate with or without additional ATG-F. One patient in the ATG-F group did not undergo transplantation, thus 201 patients who underwent transplantation with peripheral blood (n=164; 82%) or bone marrow (n=37; 18%) grafts from unrelated donors after myeloablative conditioning were included in the full analysis set, and were analysed according to their randomly assigned treatment (ATG-F n=103, control n=98). The primary endpoint was severe acute GVHD (aGVHD) grade III-IV or death within 100 days of transplantation. The trial is registered with the numbers DRKS00000002 and NCT00655343. FINDINGS: The number of patients in the ATG-F group who had severe aGVHD grade III-IV or who died within 100 days of transplantation was 12 and 10 (21.4%, 95% CI 13.4-29.3), respectively, compared with 24 and nine (33.7%, 24.3-43.0) patients, respectively, in the control group (adjusted odds ratio 0.59, 95% CI 0.30-1.17; p=0.13). The cumulative incidence of aGVHD grade III-IV was 11.7% (95% CI 6.8-19.8) in the ATG-F group versus 24.5% (17.3-34.7) in the control group (adjusted hazard ratio [HR] 0.50, 95% CI 0.25-1.01; p=0.054), and cumulative incidence of aGVHD grade II-IV was 33.0% (n=34; 95% CI 25.1-43.5) in the ATG-F group versus 51.0% (n=50; 95% CI 42.0-61.9) in the control group (adjusted HR 0.56, 0.36-0.87; p=0.011). The 2-year cumulative incidence of extensive chronic GVHD was 12.2% (n=11; 95% CI 7.0-21.3) versus 42.6% (n=34; 95% CI 33.0-55.0; adjusted HR 0.22, 0.11-0.43; p<0.0001). There were no differences between treatment groups with regard to relapse, non-relapse mortality, overall survival, and mortality from infectious causes. INTERPRETATION: The addition of ATG-F to GVHD prophylaxis with ciclosporin and methotrexate resulted in decreased incidence of acute and chronic GVHD without an increase in relapse or non-relapse mortality, and without compromising overall survival. The use of ATG-F is safe for patients who are going to receive a haematopoietic cell transplantation from matched unrelated donors. FUNDING: Fresenius Biotech GmbH.
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Authors | Jürgen Finke, Wolfgang A Bethge, Claudia Schmoor, Hellmut D Ottinger, Matthias Stelljes, Axel R Zander, Liisa Volin, Tapani Ruutu, Dominik A Heim, Rainer Schwerdtfeger, Karin Kolbe, Jiri Mayer, Johan A Maertens, Werner Linkesch, Ernst Holler, Vladimir Koza, Martin Bornhäuser, Hermann Einsele, Hans-Jochem Kolb, Hartmut Bertz, Matthias Egger, Olga Grishina, Gérard Socié, ATG-Fresenius Trial Group |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 10
Issue 9
Pg. 855-64
(Sep 2009)
ISSN: 1474-5488 [Electronic] England |
PMID | 19695955
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antilymphocyte Serum
- Immunosuppressive Agents
- Cyclosporine
- Methotrexate
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Topics |
- Adolescent
- Adult
- Antilymphocyte Serum
(administration & dosage, adverse effects)
- Cyclosporine
(administration & dosage)
- Drug Therapy, Combination
- Female
- Graft vs Host Disease
(prevention & control)
- Hematologic Neoplasms
(therapy)
- Hematopoietic Stem Cell Transplantation
(methods)
- Humans
- Immunosuppressive Agents
(administration & dosage)
- Male
- Methotrexate
(administration & dosage)
- Middle Aged
- Prospective Studies
- Regression Analysis
- Survival Analysis
- T-Lymphocytes
(immunology)
- Transplantation Conditioning
- Transplantation, Homologous
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