Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation

Patients undergoing hematopoietic stem cell transplantation (HSCT) and those with lymphoproliferative disorders (LPD) have a higher incidence of infections due to secondary hypogammaglobulinemia. One approach is the prophylactic administration of intravenous immunoglobulins (IVIG). Randomized controlled trials (RCTs) showed conflicting results in terms of type, schedule, dose and hematological patients benefiting from IVIG. We therefore performed a systematic review and meta-analysis to evaluate the role of IVIG in these patients.

To determine whether prophylaxis with IVIG reduces mortality or affects other outcomes in patients with hematological malignancies.

PubMed (January 1966 to December 2007), CENTRAL (The Cochrane Library, up to 2007, issue 1), LILACS and conference proceedings published between 2002-2007 were searched. The terms "immunoglobulins" or "gammaglobulins" or specific gammaglobulins and similar and the terms "hematologic neoplasms" or "hematologic malignancies" or "transplant" or "autotransplant" or "allotransplant" or "bone marrow transplant" or "peripheral stem cell transplant" and similar were selected. References of all included trials and reviews identified were scanned for additional trials.

All RCTs comparing prophylaxis of IVIG with placebo, no treatment or another immunoglobulin preparation, different administration schedules or doses for patients with hematological malignancies were included. One author screened all abstracts identified through the search strategy and two reviewers independently inspected each reference identified by the search and applied inclusion criteria.

For each trial, results were expressed as relative risks (RR) with 95% confidence intervals (CI) for dichotomous data and weighted mean differences for continuous data. We conducted meta-analysis, where enough similar trials were available, using the fixed- effects model, unless significant heterogeneity was present. We performed sensitivity analyses to assess the effect of individual methodological quality measures on effect estimates, including allocation generation, concealment and blinding.

Forty trials were included: thirty included HSCT patients and ten included patients LPD. When polyvalent immunoglobulins or hyperimmune cytomegalovirus (CMV)-IVIG was compared to control for HSCT, there was no difference in all-cause mortality. Polyvalent immunoglobulins significantly reduced the risk for interstitial pneumonitis but increased the risk for veno-occlusive disease and adverse events. In LPD, no benefit in terms of mortality IVIG could be demonstrated but there was a decrease in clinically and microbiologically documented infections.

In patients undergoing HSCT, routine prophylaxis with IVIG is not supported. Its use may be considered in LPD patients with hypogammaglobulinemia and recurrent infections, for reduction of clinically documented infections.