A randomized trial of high dose polyvalent intravenous immunoglobulin (HDIgG) vs. Cytomegalovirus (CMV) hyperimmune IgG in allogeneic hemopoietic stem cell transplants (HSCT).

BACKGROUND AND OBJECTIVE The role of high dose intravenous IgG (HDIgG) and of hyperimmune CMV IgG (CMV-IgG) in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT) is still unclear. The aim of this study was to compare prophylactic CMV-IgG with HDIgGin a randomized prospective trial in allogeneic HSCT recipients: primary end point of the study was the occurrence of post-transplant CMV antigenemia (CMVAg-emia). Secondary end-points were severity of acute and chronic graft-versus-host disease (GvHD), infections and transplant related mortality (TRM). DESIGN AND METHODS Patients were randomized to receive 100 mg/kg/week of CMV-IgG (group A; n = 64) or 400 mg/kg/week of HDIgG (group B; n = 64) from day -7 to day +100. The two groups were comparable for age, diagnosis, disease status, and acute graft-versus host (aGvHD) prophylaxis. RESULTS The actuarial risk at 1 year of CMV antigenemia was lower for CMV-IgG (61% vs. 71%) but not significantly (p = 0.37); CMVAg-emia occurred at the same interval from HSCT (47 vs. 48 days, p = 0.9), with a comparable number of CMVAg positive cells (3 vs. 3 p = 0.9). Eight patients died of interstitial pneumonia (IP) (4 in each group), two in group A of CMV-IP. Acute GvHD was scored as O-I, II and III-IV in 39 vs. 35, 23 vs. 22 and 2 vs. 7 patients respectively for the two groups (p = not significant). The actuarial risk of developing acute GvHD grade II-IV was lower for CMV-IgG (39% vs. 45%) but not significantly (p = 0.43). Chronic GvHD scored as absent in 7 vs. 10 patients, limited in 39 vs. 37 and extensive in 19 vs. 17 patients respectively (p = not significant). Numbered days with intravenous antibiotics, days in hospital, days of fever, number of local and disseminated infections, number of patients with fever of unknown origin were not significantly different. Actuarial 1 year TRM is 18% vs. 19%, respectively (p = 0.9). INTERPRETATION AND CONCLUSIONS This study confirms that CMV antigenemia is comparable in recipients of hyperimmune CMV-IgG and of polyvalent HDIgG, although the former had a 32% lower cost. It also shows that the potential immunomodulating effect on acute GvHD and transplant mortality is similar with 100 or 400 mg of IgG/kg/week: this is relevant, in view of the high cost of prophylactic HDIgG.