Intravenous Immunoglobulin: Appropriate Indications and Uses in Hematopoietic Stem Cell Transplantation

Intravenous immune globulin (IVIG) therapy has been prescribed in many different disease states. Hyperimmune products are also available. Recently, routine use for many indications has come under scrutiny secondary to high cost, limited supply, and unclear benefit. IVIG is U.S. Food and Drug Administration-approved for application in hematopoietic stem cell transplantation (HSCT), a very common indication for its use. In an attempt to clarify the most appropriate indications and doses in HSCT recipients, we conducted a MEDLINE search in which we reviewed all relevant articles from 1966 to the present. Search terms included bone marrow transplantation, intravenous immune globulin, hyperimmune globulin, GVHD, and cytomegalovirus (CMV). Also, the references of all pertinent studies and review articles were scanned for studies missed via MEDLINE. CMV prophylaxis/treatment and GVHD prophylaxis are the 2 indications with the most significant clinical support, but there are very few prospective, randomized, controlled trials reported. Furthermore, sample size usually was small, included heterogeneous patient populations, and employed different primary end points. Several reports support IVIG therapy in combination with ganciclovir for prevention and treatment of CMV infection, whereas others have shown ganciclovir monotherapy to be effective, blurring the benefit of IVIG administration. CMV IgG data are also imprecise and difficult to interpret. The role of IVIG therapy in prevention and treatment of GVHD also is vague. Only 1 randomized investigation showed a benefit in the prevention of acute GVHD, and no studies showed efficacy in chronic GVHD prophylaxis and therapy. Reports examining the utility of IVIG or CMV IgG in HSCT are hampered by marked variation in trial design and dosing and diverse patient characteristics. Although IVIG may be useful as a component of preemptive therapy and treatment of CMV disease, its contribution to the prevention of reactivation of CMV infection is dubious. Extended IVIG therapy during GVHD prevention may impair recovery of humoral immunity, and its role in prophylaxis and therapy of GVHD has not been clearly defined. Hospital monitoring programs may be a valuable way to detect areas of high use and allow for streamlining of prescribing.