Benefits Balanced with Harm

Intravenous Immunoglobulin (IVIG)

for Prevention of Infection: General

Immunoglobulin is an antibody in the immune system that identifies and neutralizes foreign items such as bacteria and viruses. It is part of the humoral immune system. Prophylactic IV administration of immunoglobulin (IVIG) has been examined in patients with cancer for prevention of infection. In general, consideration of IVIG is only suggested by NCCN guidelines for patients with significant hypogammaglobulinemia.

Systematic Review/Meta-Analysis

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.

Purpose

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.

Search Strategy

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

Literature Evaluated

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.

Sample Characteristics

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.

Results

  • 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.

Conclusions

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

Limitations

  • 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.

Nursing Implications

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

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Guideline / Expert Opinion

National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Prevention and treatment of cancer-related infections [v.2.2011]. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf

Purpose & Patient Population

To provide guidance for clinical practices for the prevention and treatment of infection in patients with cancer.

Type of Resource/Evidence-Based Process

This resource is a consensus-based guideline.

Phase of Care and Clinical Applications

Patients were undergoing the active antitumor treatment phase of care.

Guidelines & Recommendations

The guideline

  • Recommends the consideration of general antibacterial prophylaxis in patients at intermediate and high risk for infection, consideration of antifungal prophylaxis during neutropenia and for anticipated mucosits, and antiviral prophylaxis for intermediate- and high-risk patients.
  • Provides suggestions for specific agents for prophylaxis and treatment in various clinical scenarios.
  • Outlines treatment and diagnostic/assessment approaches for neutropenic fever and specific clinical presentations.
  • Notes that chlorhexidine and sliver sulfadiazine-coated short-term central catheters have been shown to decrease the incidence of catheter colonization and bloodstream infections, but not in patients with hematologic malignancies requiring indwelling catheters for approximately 20 days.
  • Notes that vaccination recommendations for transplantation recipients and their household members should be performed.
  • Recommends the pneumococcal vaccine in asplenic patients.

The National Comprehensive Cancer Network (NCCN) does not currently endorse the use of a vancomycin lock solution for long-term vascular access devices due to concerns about the emergence of bacterial resistance if widely used. Influenza vaccination with a vaccine that does not use live attenuated organisms can be safely given, and the guideline recommends administration at least two weeks before receiving cytotoxic therapy.

Limitations

This study lacked high-quality evidence, with most recommendations being based on consensus.

Nursing Implications

This guideline provided comprehensive references to assess patient risk of infection and expert recommendations regarding interventions aimed at the prevention and treatment of infection in patients with cancer. The guideline does not discuss long-term survivorship issues in this area.

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