Use of Cytomegalovirus Intravenous Immune Globulin for the Adjunctive Treatment of Cytomegalovirus in Hematopoietic Stem Cell Transplant Recipients

Abstract

Study Objective To describe characteristics and clinical outcomes of hematopoietic stem cell transplant (HSCT) patients who received adjunctive Cytomegalovirus Intravenous Immune Globulin (CMV-IVIG) for probable or proven cytomegalovirus (CMV) disease. Design Retrospective cohort study. Setting A large, university-affiliated, tertiary-care medical center. Patients Thirty-five adult HSCT patients receiving at least one dose of CMV-IVIG for adjunctive treatment of probable or proven CMV disease over an eight-year period. Measurements and Main Results All-cause mortality at hospital discharge was the primary outcome. All patients received an allogeneic HSCT. Twenty-six patients had pneumonitis (74%), nine had enteritis (26%), and 29 had CMV viremia (83%). All patients received concomitant antiviral therapy; 31 (89%) received ganciclovir and 14 (40%) received foscarnet. All-cause mortality at hospital discharge was 49%. Patient characteristics associated with mortality included requiring intubation for CMV pneumonia (79% of non-survivors vs. 25% of survivors, p=0.016) and earlier disease onset following HSCT (median of 48 days for non-survivors vs. 106 days for survivors, p<0.001). In multivariable analysis, only requiring intubation for CMV pneumonia remained a significant risk factor for increased mortality. CMV-IVIG was attributed with a low rate of adverse events; mild hypertension (5.7%) and erythema/chills (2.9%) were most common. Conclusions The mortality rate in our population is similar to previous reports in the literature, and may be somewhat lower than rates reported with antiviral monotherapy. Our analysis suggests that factors associated with mortality include the need for intubation and, possibly, earlier onset of CMV disease following HSCT. CMV-IVIG appears to be well-tolerated in HSCT patients. These findings support further trials of CMV-IVIG efficacy in this setting.

Management of Acute Respiratory Failure in Patients With Hematological Malignancy

“…The treatment of choice is ganciclovir or foscarnet 38 . CMV-specific immunoglobulin (CMV-IVIG) has been used for the treatment of CMV pneumonitis in allogeneic transplant recipients, and it may improve outcomes if used in combination with antiviral therapy 39 . Adenovirus infections 40 in transplant recipients are increasingly recognized as significant causes of morbidity and mortality.…”

Infectious Diseases and the Kidney in Children

“…Use of other antiviral agents such as foscarnet and cidofovir is limited because of nephrotoxicity and difficulty of administration. The role of high-titer CMV immunoglobulin therapy in reducing severe CMV-associated disease after stem cell transplant remains unclear [119].…”

Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus

“…The use of HCMV-specific immunoglobulins (Iv-Ig) to treat transplant patients and mothers who have active HCMV infections indicate that Iv-Ig has a clinical benefit [104][105][106][107][108]. However, the results of these studies have been met with a certain amount of controversy [109,110].…”

“…Furthermore, in transplant patients, the vaccine was able to induce significant levels of neutralising gB antibody, and this had an inverse correlation with the duration of viraemia [128]. However, whilst neutralising antibodies do not always lead to reduced viral load, Iv-Ig, which contains both neutralising and non-neutralising antibodies, can reduce disease burden, suggesting that CMV-specific IgG can elicit effective immune responses besides virus neutralization [104,108].…”