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 - 11/08/11
, Wolfgang A Bethge, MD b, Claudia Schmoor, PhD c, Hellmut D Ottinger, MD d, Matthias Stelljes, MD e, Axel R Zander, ProfMD f, Liisa Volin, MD g, Tapani Ruutu, MD g, Dominik A Heim, MD h, Rainer Schwerdtfeger, ProfMD i, Karin Kolbe, MD j, Jiri Mayer, ProfMD k, Johan A Maertens, MD l, Werner Linkesch, ProfMD m, Ernst Holler, ProfMD n, Vladimir Koza, ProfMD o, Martin Bornhäuser, ProfMD p, Hermann Einsele, ProfMD q, Hans-Jochem Kolb, ProfMD r, Hartmut Bertz, ProfMD a, Matthias Egger, MD a, Olga Grishina, MD c, Gérard Socié, ProfMD, PhD sfor the ATG-Fresenius Trial Group‡
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<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.
Le texte complet de cet article est disponible en PDF.Plan
Vol 10 - N° 9
P. 855-864 - septembre 2009 Retour au numéro
Article précédent
- Standard versus pH-adjusted and lidocaine supplemented radiocolloid for patients undergoing sentinel-lymph-node mapping and biopsy for early breast cancer (PASSION-P trial): a double-blind, randomised controlled trial
- Alexander Stojadinovic, George E Peoples, Jennifer S Jurgens, Robin S Howard, Brandi Schuyler, Kyung H Kwon, Leonard R Henry, Craig D Shriver, Chester C Buckenmaier
- Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials
- Chantal Quinten, Corneel Coens, Murielle Mauer, Sylvie Comte, Mirjam AG Sprangers, Charles Cleeland, David Osoba, Kristin Bjordal, Andrew Bottomley, on behalf of the EORTC Clinical Groups
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?