Oral administration of IgG in marrow transplant recipients.

TOTHE EDITOR: Infection is an important obstacle to the long-term survival of many bone marrow transplant (BMT) recipients. Yolken et al. demonstrated that 40 percent of transplant patients were infected with enteric pathogens including adenovirus, rotavirus, coxsackie virus, and Clostridium difficile.' The mortality among the infected patients was 55 percent compared with 13 percent among the noninfected patients. In addition, the gastrointestinal tract is a common entry site for agents that cause systemic infection. Measures that could prevent or treat such infections might reduce the mortality associated with bone marrow transplantation. Although it has been reported that orally administered immunoglobulin G (IgG) is rapidly degraded in the normal gastrointestinal tract, Snodgrass et al. have demonstrated that IgG is effective when given orally to rotavirus-infected Iambs.' Other studies have demonstrated effectiveness in modifying rotavirus infection when gamrnaglobulin is administered to low birthweight infants.' The oral administration of an IgA-lgG preparation lowered the incidence of necrotizing enterocolitis in low birthweight infants.t It appears that IgG exerts a protective effect through its opsonizing and antitoxic properties.' We report here the results of a pilot study of orally administered gammaglobulin in allogeneic BMT recipients. Thirty patients, aged 15-50 years, undergoing allogeneic marrow transplantation for leukemia or lymphoma were consecutively entered into the study. All patients received immune serum globulin 50 mg/kg/body weight po (Sandoglobulin, Sandoz Pharmaceuticals) reconstituted with NaCl 0.9"70 in 4 divided doses daily beginning 2 days following transplantation and continuing for 28 days posttransplantation. Aliquots of stool were collected 8 days prior to transplantation (I day prior to beginning a conditioning regimen of busulfan and cyclophosphamide), on the day following transplantation, and then weekly until day 36. Stool was routinely cultured for viral pathogens and tested by enzymelinked immunosorbent assay for rotavirus. Approximately 2 ml of buffer (barbital sodium pH 8.8) was mixed with I ml of stool in an ultracentrifuge tube, mixed well, and placed on a blood rocker for 30 minutes. The specimen was ultracentrifuged for 45 minutes at 20 000 rpm at 4°C. The supernatant was placed into a 12 x 75 mm glass tube. IgG was quantitated on a Beckman rate nephelometer. Only two patients missed more than a single day's administration of IgG due to nausea. No other toxicity was noted. As expected, none of the patients studied had stool IgG detected prior to initiation of the preparative regimen or immediately following completion of the regimen prior to IgG administration. During the period of administration, 20 of the 27 patients demonstrated stool IgG. Eighteen had a stoollgG concentration >20 mg/dL during the course of IgG administration. The highest stoollgG concentration among these patients ranged from 6 to 400 mg/dL (median 40 mg/dL). Only two patients had IgG detected one week following completion of globulin administration and only six developed significant (2 grade 2 of 4) acute graft-versus-host disease. Only one patient had a viral pathogen (adenovirus) cultured from the stool. Ten of the 27 patients did not require therapeutic antibiotic administration; only one developed documented bacteremia. This study demonstrates that orally administered gammaglobulin is well tolerated and that substantial amounts survived passage through the gastrointestinal tract of BMT recipients. It is well established that chemotherapy is cytotoxic to B cells and profoundly impairs antibody formation." This impairment significantly compromises the patient's ability to fight infection. A decreased concentration of antibody to core glycolipid of Enterobacteriaceae has been demonstrated in patients with malignancy who die of gram-negative septicemia." .e Because the majority of infections in neutropenic patients arise from endogenous flora, especially from the gastrointestinal tract, oral treatment with immunoglobulins may have profound effects on the incidence of systemic infections as well as gastroenteritis. A randomized, placebo-controlled, double-blind trial to determine the effectiveness of this treatment is underway at Ohio State University. EDWARD A. COPELAN, M.D. Division ofBone Marrow Transplantation Department of Internal Medicine TOM BECHTEL, Pharm.D. Department ofPharmacy NANCYC. FEATHERINGHAM,A.M.T. MARY M. GROSE, A.S.C.P., S.1. DANIEL D. SEDMAK, M.D. Clinical Immunology Department ofPathology NEENA KAPOOR, M.D. PETER 1. TUTSCHKA, M.D. Division ofBone Marrow Transplantation Department ofInternal Medicine Ohio State University Columbus, Ohio 43210