Does high-dose intravenous immune globulin treatment after bone marrow transplantation increase mortality in veno-occlusive disease of the liver?

Forty-five recipients of bone marrow from HLA-identical siblings were given intravenous immune globulin (IVIG) 0.5 g/kg once a week during the first 3 months after transplantation. Fifty-three consecutive previously transplanted HLA-identical siblings were included as controls. Only patients who were cytomegalovirus (CMV) seropositive or had a CMV-seropositive donor were included. There were no major differences in patient characteristics between the two groups. However, more patients in the IVIG group received individualized graft-versus-host disease (GVHD) prophylaxis with less cyclosporine (P < 0.01), more controls received liposomal amphotericin B (P = 0.01), and more patients in the IVIG group received low-dose heparin as prophylaxis against veno-occlusive disease of the liver (P < 0.001). Median follow-up was 21 months in the IVIG group and 47 months in the control group. There were no differences between the groups with regard to time to engraftment, hospitalization time, or days with fever. No differences between the IVIG group and control group were detected in the incidence of acute GVHD grade II-IV (17% vs. 23%) or chronic GVHD (30% vs. 42%). The incidence of bacterial septicemias (53% vs. 63%) and invasive fungal infections (9% vs. 6%) was unaffected by IVIG treatment. The incidence of symptomatic CMV infection was the same in the two groups (14% vs. 16%). One control patient died of CMV interstitial pneumonitis, and 1 patient from each group died from viral interstitial pneumonitis of other origin. The incidence of veno-occlusive disease (VOD) was 16% in the IVIG group versus 6% in the controls (P = NS). Fatal VOD occurred in 11% of the IVIG group compared with none of the controls (P = 0.02). Other transplant-related complications did not differ between the two groups. Two-year survival was 62% in the IVIG group and 60% in the controls (P = NS). No significant beneficial effect was seen with IVIG, which may increase mortality in VOD. The use of high dose IVIG as prophylaxis in marrow transplant recipients is questioned.