Cytomegalovirus Immune Globulin Prophylaxis in Liver Transplantation

A Randomized, Double-blind, Placebo-controlled Trial

15 November 1993 | Volume 119 Issue 10 | Pages 984-991

Objective: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants.

Design: Randomized, multicenter, placebo-controlled, double-blind trial.

Setting: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation).

Patients: One hundred forty-one liver transplant recipients completed the study.

Intervention: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16.

Measurements: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness.

Results: Using a Cox proportional-hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group).

Conclusion: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Author and Article Information

From New England Medical Center, Massachusetts General Hospital, New England Deaconess Hospital, Children's Hospital, and Massachusetts State Laboratory Institute, Tufts University School of Medicine, and Harvard Medical School, Boston, Massachusetts.
Requests for Reprints: David R. Snydman, MD, Box 238, New England Medical Center, 750 Washington Street, Boston, MA 02111.
Acknowledgments: The authors thank Roselia Martinez for preparation of the manuscript and Yvonne Gonzalez, Laurie Gibbons, Fay Gitlin, Karen Chen, and Sandy Monticello for technical assistance.
Grant Support: By grant R10 DK31389 from the National Institutes of Health.