Raanani, P., Gafter-Gvili, A., Paul, M., Ben-Bassat, I., Leibovici, L., & Shpilberg, O. (2009). Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: Systematic review and meta-analysis. Leukemia and Lymphoma, 50, 764–772.

The purpose of the article is to examine whether prophylactic administration of IV immunoglobulin (IVIG) reduces mortality, major infections, and the rate of documented microbial infection in patients with lymphoproliferative and plasma cell disorders.

The PubMed, Cochrane Library, and LILACS databases as well as numerous conference proceedings published from 2002–2008. Hand searching of references was also done.

Key words were immunoglobulins, gammaglobulins, specific gammaglobulins names, hematologic neoplasms, or hematologic malignancies, multiple myeloma, plasma cell dyscrasias, leukemia, lymphoma or lumphoproliferative disorders.

Inclusion criteria:

• Randomized, controlled trials comparing an IVIG preparation with placebo, no treatment, another immunoglobulin preparation, or a different administration schedule or dose
• Patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, cutaneous lymphomas or Hodgkin lymphoma, monoclonal gammopathy, multiple myeloma, amyloidosis, Waldenstrom macroflobulinemia, cryuglobulinemia, or heavy chain disease.
• Any publication type
• Any language

The search strategy identified 613 trials. Trials were graded according to allocation concealment according to the Cochrane Handbook guidelines. Sixteen trials were considered relevant and included in the initial review. Seven of these were excluded due to duplication, route of administration, and study design.

The final sample included in the systematic review was nine studies. Five studies had usable information for meta analysis. Study samples ranged from 16–42, and the review included a total sample of 408 patients across all studies.

• Only two trials reported all cause mortality at one year, and both showed no difference between study groups.
• There was a statistically significant reduction in occurrence of major infection (RR = 0.45, 95% CI [0.27, 0.75])
• There was a significant, 51% reduction in all clinically documented infections with IVIG (RR = 0.49, 95% CI [0.39, 0.61])
• Polyvalent IVIG was associated with a significant increase in adverse events (RR = 2.37, 95% CI [1.74, 3.24]). Side effects included allergic reactions with anaphylaxis, fever, chills, and gastrointestinal complaints. Adverse events rarely required discontinuation of treatment.

Use of IVIG did not appear to affect overall mortality. The rate of major infections requiring inpatient treatment was significantly lowered by IVIG prophylaxis.

• Reviewed studies were old, done in the 1990s and since that time patient populations and therapeutic protocols have changed. 
• Implications of these findings in the context of current clinical practice are unclear.
• Different trials used different IVIG preparations from various companies, and varied doses were used. 
• These differences could have affected the comparison of trial outcomes in this meta-analysis.

Based on these results, contemporary studies of IVIG prophylaxis are warranted.