Should immunoglobulin therapy be used in allogeneic stem-cell transplantation?: A randomized, double-blind, dose effect, placebo-controlled, multicenter trial

Background: 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. Objective: To assess the role and the close-effect relationship of immunoglobulin in the prophylaxis of complications after allogeneic stem-cell transplantation. Design: Multicenter randomized, double-blind, dose effect placebo-controlled study. Setting: 19 stem-cell transplantation centers in France. Patients: 200 patients who had allogeneic stem-cell transplantation from HLA-identical sibling donors between 1998 and 2000. Intervention: 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. Measurements: 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. Results: 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). Conclusions: Use of prophylactic immunoglobulin in allogeneic recipients of stem-cell transplant from HLA-identical sibling donors is not recommended.