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

Summary Background Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors. Anti-T-cell globulins (ATGs) might lower the incidence of GVHD. We did a prospective, randomised, multicentre, open-label, phase...

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Published in:The lancet oncology 2009-09, Vol.10 (9), p.855-864
Main Authors: Finke, Jürgen, Prof, Bethge, Wolfgang A, MD, Schmoor, Claudia, PhD, Ottinger, Hellmut D, MD, Stelljes, Matthias, MD, Zander, Axel R, Prof, Volin, Liisa, MD, Ruutu, Tapani, MD, Heim, Dominik A, MD, Schwerdtfeger, Rainer, Prof, Kolbe, Karin, MD, Mayer, Jiri, Prof, Maertens, Johan A, MD, Linkesch, Werner, Prof, Holler, Ernst, Prof, Koza, Vladimir, Prof, Bornhäuser, Martin, Prof, Einsele, Hermann, Prof, Kolb, Hans-Jochem, Prof, Bertz, Hartmut, Prof, Egger, Matthias, MD, Grishina, Olga, MD, Socié, Gérard, Prof
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antilymphocyte Serum - administration & dosage
Antilymphocyte Serum - adverse effects
Cyclosporine - administration & dosage
Drug Therapy, Combination
Female
Graft vs Host Disease - prevention & control
Hematologic Neoplasms - therapy
Hematology, Oncology and Palliative Medicine
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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Summary:Summary Background Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors. Anti-T-cell globulins (ATGs) might lower the incidence of GVHD. We did a prospective, randomised, multicentre, open-label, phase 3 trial to compare standard GVHD prophylaxis with ciclosporin and methotrexate with or without anti-Jurkat ATG-Fresenius (ATG-F). 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
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(09)70225-6