Catherine Cordonnier, MD, PhD; Sylvie Chevret, MD, PhD; Marc Legrand; Homa Rafi, MD; Nathalie Dhdin, MD; Blandine Lehmann, PharmD; Franois Bassompierre, MD; Eliane Gluckman, MD, PhD; for the GREFIG Study Group*
The authors dedicate this article to Claude Chastang, MD, PhD, a friend and colleague whose vision and leadership have been cornerstones in the design and development of therapeutic trials in France. He played a major role in the design of this study. His friendship will be missed.
Acknowledgment: The authors thank the physicians, pharmacists, data managers, and nurses of the participating centers and the support staff of the Dlgation de la Recherche Clinique, Hpital Saint-Louis, Paris. The authors also thank Dr. Isabel Cunningham for her critical reading of the manuscript and Dr. Per Ljungman for his useful comments.
Grant Support: By the French Ministry of Health (PHRC 96029), Assistance Publique-Hpitaux de Paris (GERMED 1996), and the Caisse Nationale d'Assurance Maladies des Professions Indpendantes.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Catherine Cordonnier, MD, Service d'Hmatologie Clinique, Hpital Henri Mondor, 51, Av. Marchal de Lattre de Tassigny, 94000 Crteil, France; e-mail, email@example.com.
Current Author Addresses: Drs. Cordonnier and Rafi: Service d'Hmatologie Clinique, Hpital Henri Mondor, 51, Av. Marchal de Lattre de Tassigny, 94000 Crteil, France.
Dr. Chevret: Dpartement de Biostatistique et Informatique Mdicale, Hpital Saint-Louis, 1, Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Mr. Legrand: Dpartement d'Information Mdicale, Hpital Robert Debr, 49, Boulevard Serurier, 75019 Paris, France.
Dr. Dhdin: Service d'Hmatologie, Hpital Piti-Salptrire, 47-83, Boulevard de l'hpital, 75013 Paris, France.
Dr. Lehmann: Unit Essais Cliniques, Etablissement Pharmaceutique des Hpitaux de Paris, 7, rue du Fer Moulin, 75005 Paris, France.
Dr. Bassompierre: Dlgation Rgionale la Recherche Clinique, Hpital Saint-Louis Aile Hillairet, 1, Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Dr. Glckman: Unit de Greffe de Moelle, Hpital Saint-Louis, 1, Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Author Contributions: Conception and design: C. Cordonnier, F. Bassompierre, E. Gluckman.
Analysis and interpretation of the data: C. Cordonnier, S. Chevret.
Drafting of the article: C. Cordonnier.
Critical revision of the article for important intellectual content: H. Rafi, B. Lehmann.
Final approval of the article: C. Cordonnier, S. Chevret, E. Gluckman.
Provision of study materials or patients: C. Cordonnier, H. Rafi, N. Dhdin, B. Lehmann.
Statistical expertise: S. Chevret.
Obtaining of funding: C. Cordonnier, F. Bassompierre, E. Gluckman.
Administrative, technical, or logistic support: M. Legrand, H. Rafi, B. Lehmann, F. Bassompierre.
Collection and assembly of data: M. Legrand.
The universal use of prophylactic immunoglobulin in stem-cell transplantation has not been supported by strong evidence of benefit. Results of most trials were reported before effective drugs for cytomegalovirus infection and disease were available, and no trial was placebo controlled.
To assess the role and the dose-effect relationship of immunoglobulin in the prophylaxis of complications after allogeneic stem-cell transplantation.
Multicenter randomized, double-blind, dose effect placebo-controlled study.
19 stem-cell transplantation centers in France.
200 patients who had allogeneic stem-cell transplantation from HLA-identical sibling donors between 1998 and 2000.
Immunoglobulin at doses of 50 mg/kg of body weight, 250 mg/kg, or 500 mg/kg weekly from day 7 to day 100 after transplantation or placebo.
Cumulative incidence of infection, graft-versus-host disease, veno-occlusive disease, interstitial pneumonia, and transplantation-related mortality at 6 months; overall survival at 2 years after transplantation.
Immunoglobulin had no benefit over placebo; 92% of patients in the pooled immunoglobulin group and 90% of patients in the placebo group had one or more infections (difference, 2 percentage points [95% CI, 8 to 12 percentage points]). Cumulative incidences of interstitial pneumonia, graft-versus-host disease, transplantation-related mortality, and overall survival were similar in patients receiving placebo and those receiving immunoglobulin; no dose-effect relationships were evident. Grade 3 (severe) veno-occlusive disease occurred more frequently as the immunoglobulin dose increased (P = 0.01).
Use of prophylactic immunoglobulin in allogeneic recipients of stem-cell transplant from HLA-identical sibling donors is not recommended.
*For investigators and participating centers for the GREFIG Study Group, see the Appendix.
Catherine Cordonnier, Sylvie Chevret, Marc Legrand, Homa Rafi, Nathalie Dhdin, Blandine Lehmann, et al. Should Immunoglobulin Therapy Be Used in Allogeneic Stem-Cell Transplantation?: A Randomized, Double-Blind, Dose Effect, Placebo-Controlled, Multicenter Trial. Ann Intern Med. 2003;139:8–18. doi: 10.7326/0003-4819-139-1-200307010-00007
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Published: Ann Intern Med. 2003;139(1):8-18.
Hematology/Oncology, Interstitial Lung Disease, Pulmonary/Critical Care.
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