A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery
Biology of Blood & Marrow Transplantation. 1996;2((1):):44-53.
To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.
Early infectious complications in allogeneic marrow transplant recipients with acute leukemia: effects of prophylactic measures
One hundred eighty-two patients with acute leukemia underwent allogeneic marrow transplantation and received one of two forms of infection prophylaxis: isolation and decontamination procedures in laminar air flow rooms (90 patients) or prophylactic granulocyte transfusion from a single family member (92 patients). Infection acquisition and survival were analyzed from the time of admission to 100 days posttransplant. There were 20 major local infections in the laminar air flow group and 16 in the prophylactic granulocyte group. Of the patients in the laminar air flow group, 24 (27%) had 27 episodes of bacteremia, while 23 (25%) of the prophylactic granulocyte group had 25 episodes of bacteremia. There were no significant differences in infection acquisition between the two groups during the period of granulocytopenia or after engraftment. The mortality during the first 100 days was 28% for the laminar air flow group and 35% for the prophylactic granulocyte group. Thirteen patients (14%) in the laminar air flow group and five (5%) in the prophylactic granulocyte group died with bacterial or fungal infections. There were no statistically significant differences between the two groups in overall incidence of or mortality from interstitial pneumonitis which was the predominant cause of death. However, the subset of patients who were seronegative for cytomegalovirus antibody at the time of transplant and received granulocytes from seropositive donors had a significantly higher incidence of and mortality from cytomegalovirus interstitial pneumonitis.
Granulocyte transfusions for the prevention of infection in patients receiving bone-marrow transplants
New England Journal of Medicine. 1978;298((19):):1052-7.
Prophylaxis by granulocyte transfusions against infection associated with granulocytopenia was studied in 69 patients receiving bone-marrow transplants for the therapy of hematologic neoplasia or aplastic anemia. Patients were randomized to receive or not to receive granulocyte transfusions when their circulating granulocyte levels fell to less than 200 per cubic millimeter during the period between transplantation and the development of graft function. During the first 21 posttransplant days, there were two local infections and no septicemias in 29 transfused patients. Seven local infections and 10 septicemias developed among the 40 controls. This protection was afforded by granulocytes collected by reversible leukoadhesion as well as by cells collected by continuous-flow centrifugation.