The impact of CMV after transplantation is well recognized; however, the optimal regimens to prevent CMV infection and disease, as well as their direct and indirect effects, remain difficult to identify. In pediatric lung transplant, the impact of adding CMVIG to standard antiviral prophylaxis has not been previously explored. The risks for CMV infection and disease in this cohort are similar to those reported previously in both the adult and pediatric literature, with increased risk during the early transplant era and with donor/recipient CMV seropositivity [5
Similar to previously reported assessments of risks, the data collected in this study indicate that ganciclovir prophylaxis along with CMVIG as adjunct therapy was associated with a decreased risk of CMV infection but not CMV disease within the first year after pediatric lung transplantation. In addition, CMVIG did not appear to impact occurrence of acute rejection, BOS, or survival. Results reported from adult lung transplant recipients have been variable with decreased CMV infection and/or disease without a control group or with historical controls [24
]. Alternatively, some reports in adult liver transplant recipients have demonstrated that administration of CMVIG resulted in decreased episodes of tissue-invasive CMV disease [10
]. Additional studies in liver transplant recipients from the same group reported that the addition of ganciclovir to CMVIG is superior to CMVIG alone and is cost effective [26
]. Similarly, in adult heart transplant patients, CMVIG alone can decrease the risk of CMV disease [28
]; further, the prophylactic administration of CMVIG with ganciclovir significantly reduced rates of CMV disease in comparison to rates in those who received ganciclovir alone[9
]. The difference between the results in the pediatric lung transplant population, which does not have a decrease in CMV disease but does have a decrease in CMV infection, may be related to the definitions applied in this study compared to those previously reported studies as many were performed prior to the development of the currently accepted definitions that were used in this study.
More recent analyses indicate that CMVIG administration decreases CMV-related morbidity and mortality [3
]. The benefit conferred may be due either to a correction of hypogammaglobulinemia or directly from CMV prevention or amelioration, but this has not been investigated [29
]. In this cohort, CMVIG administration was not associated with decreased CMV-related morbidity or mortality. The observational nature of this cohort including a lack of uniformity for the schedule and dosage of CMVIG prevent drawing definitive conclusions.
As with any retrospective cohort, limitations regarding the available data exist. In this study, information regarding immunoglobulin levels was not recorded; however at the time of data collection, no center routinely collected serial measurement of immunoglobulin levels in their patients for the duration of the study period. As with previously reported data from this cohort, the definitions for risks and outcomes applied were determined prior to the initiation of data collection and were applied uniformly across all participating sites.
As reported above, the participating centers did not use a standard dosing schedule for CMVIG. Possible explanations for the wide range of dosing schedules include duration of the study period, variability in clinician preference and the lack of centrally available standardized dosing regimens. However, details of CMVIG administration, including date of infusion and dosing regimens, were captured through substantive review of pharmacy records and clinical charts. Descriptive information regarding the administration of CMVIG in the 62 pediatric lung transplant recipients who received the therapy is presented for inference. In addition, with the follow-up ending at one year post-transplant, associations with remote outcomes including BOS may be underestimated by this analysis.
The impact of concurrent ganciclovir administration also requires comment. To limit the complexity of the analysis, subjects who received less than three weeks or no ganciclovir prophylaxis were excluded from the analysis. In addition, subjects who received CMVIG also received a slightly longer average duration of ganciclovir which was statistically significant (2.9 months verses 1.6 months). However, the addition of prophylaxis duration to the multivariable models did not significantly alter the models.