Graft-vs.-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Intravenous immunoglobulin (IVIg) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD, interstitial pneumonia, and infection in adults early after allogeneic transplantation. The current study is a controlled trial to determine whether a lower total dose of IVIg given
with pretransplant loading reduces the incidence of transplant-related complications. In a randomized trial of 241 patients > or =20 years of age who were given related donor marrow allografts, 121 individuals receiving Ig prophylaxis (500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90) were compared with 120 control patients who did not receive IVIg. Randomization was stratified by human leucocyte antigen-matching, remission status of malignancy, GVHD prophylaxis, and cytomegalovirus (CMV) serology. The study was powered to detect a reduction in acute GVHD by 18% and a decrease in transplant-related mortality by 17%. Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels >1350 mg/dL, which were approximately twofold greater than the untreated controls (p<0.01). White blood cell and platelet recoveries were similar for the two groups, although control patients required fewer units of platelets per day (2.5 vs. 3.3, p = 0.008). No significant differences in the incidence of CMV infection, interstitial pneumonia, or bacteremia were observed. The incidence of acute GVHD did not differ between the two groups; however, acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels >3000 mg/dL (60 vs. 79%). Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis. However, the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls (31 vs. 18%, p = 0.03). Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg (p = 0.021). We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants. Note, IVIg administration may be associated with an increased risk of recurrent malignancy, a finding that warrants further investigation.