Cytomegalovirus Immunoglobulin Decreases the Risk of Cytomegalovirus Infection but not Disease After Pediatric Lung Transplantation

Abstract

A retrospective review of pediatric lung transplant recipients at fourteen sites in North America and Europe was conducted to evaluate the impact of adding cytomegalovirus immunoglobulin (CMVIG) prophylaxis to at least three weeks of intravenous ganciclovir in pediatric lung transplant recipients. Data were recorded for the first year after transplantation. Associations between time to CMV and risk factors, including CMVIG use, were assessed by multivariable Cox proportional hazards models. Of 599 subjects whose charts were reviewed, 329 received at least three weeks of ganciclovir with 62 (19%) receiving CMVIG. CMVIG was administered more frequently with CMV donor-positive/recipient-negative (D+/R−) serostatus (p<0.05). In multivariable models, subjects who did not receive CMVIG as part of their prophylaxis were three times more likely to develop CMV infection (HR 3.4; 95% CI 1.2, 9.5) independent of CMV serostatus. However, CMVIG administration was not associated with decreased risk of episodes of CMV disease. Receipt of CMVIG was not associated with decreased risks of post-transplant morbidities (acute rejection, respiratory viral infection or early bronchiolitis obliterans) or morbidity within the first year after pediatric lung transplantation. The use of CMVIG in addition to antiviral prophylaxis in pediatric lung transplantation requires further evaluation in pediatric lung transplant recipients.

Updated International Consensus Guidelines on the Management of Cytomegalovirus in Solid-Organ Transplantation

“…Krampe et al found a low incidence of CMV disease in 28 pediatric liver transplant recipients receiving IVIG and preemptive therapy but did not have a comparison group (241). In a retrospective review of 329 pediatric lung transplant recipients, of whom 62 (19%) received CMV Ig in addition to at least 3 weeks of intravenous ganciclovir, CMV Ig was associated with a decreased risk of CMV infection but did not impact the incidence of CMV disease, acute rejection, or early morbidity (243). In one prospective randomized pediatric study that primarily targeted Epstein-Barr virus, CMV Ig did not appear to have a significant impact on the development of CMV disease, although there was a trend toward a higher 2-year CMV disease-free rate in R+ children (216).…”

Human cytomegalovirus (HCMV)‐specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid‐organ transplant recipients

“…However, this protective effect of mAbs was observed in seronegative patients, whereas our study is focused on seropositive recipients. While observational studies reported conflicting results, 2 randomized studies reported protection against both infection and disease . In addition, a meta‐analysis study conducted a few years ago, which analyzed 11 randomized SOTR trials (about 700 patients), reported that HCMV IG administration was associated with improved survival, reduced HCMV disease and HCMV‐associated death …”

“…The protective effect of antibodies was suggested by experimental findings in the mouse CMV model, where lethal infection in immune‐deficient mice was prevented . Similarly, in SOTR, several observational studies have claimed the protective effect of IG against HCMV infection, in addition to a partial protection from HCMV disease and improved survival both in adult and pediatric patients receiving thoracic, kidney, or liver transplant . Randomized trials provided discordant results on the efficacy of IG in seronegative recipients of kidney or liver from seropositive donors (thus, at risk for primary infection), whereas a recent randomized trial showed the efficacy of mAbs in preventing HCMV disease in seronegative kidney recipients …”

Cytomegalovirus Infections in Pediatric Solid Organ Transplant Patients

“…İmmünglobulin tedavisi (IVIG (intravenöz immünglobulin) ve CMVIG (CMV immünglobulin)) hem önlem stratejileri içinde hem de CMV hastalığında yeri tartışmalı bir uygulamadır. NAPRTCS çalışmasında CMVIG profilaksisinin IVIG+antiviral tedaviye göre CMV hastalığına bağlı hastaneye yatış sıklığını azalttığı gösterilse de sonraki çalışmalarda bu yöntemin CMV enfeksiyonunu azalttığı ancak CMV hastalığını azaltmadığı gösterilmiştir (60).…”