4 | Discussion
Given the inconsistent status of the relationship between pre-transplant RVI and post-transplant outcomes, this study aimed to elucidate the importance of pre-transplant RV PCR screening to avoid post-transplant morbidity and mortality. This study included a cohort of 170 pediatric HSCT patients. We found that pre-transplant RVI was positively correlated with post-transplant mortality and requirement for ICU transfer in the first 100 days post-transplant. These associations remained after multivariate analysis.
The relationship between pre-transplant RVI and transplant-related mortality (TRM) has been examined in prior past studies. Some retrospective analyses of adult allogeneic HSCT patients did not find an association between pre-transplant RV detection and increased mortality.16, 20 This apparent lack of association between pre-transplant RVI and transplant-related complications and mortality was not found in upper respiratory, lower-risk infections such as coronaviruses and rhinovirus. However, an association between increased mortality and hospitalization and testing positive pre-transplant for the higher-risk RVIs, especially those causing lower-respiratory disease (LRD). The presence of LRD of any type of virus, including HRV alone, was confirmed to be associated with increased mortality, but only in conjunction with pre-transplant myelosuppression.15 In a pediatric retrospective survey of the same subject, Kim et al (2017) found an association between pre-transplant RVI and hospitalization but not with transplant-related mortality. One explanation for this difference in findings is that they included RVI PCR test results up to 90 days before HSCT,13 whereas our study had a narrower range of days from which we collected PCR results. Like our study, Ottaviano et al found a significant increase in post-transplant mortality when pediatric patients underwent HSCT in the setting of a respiratory virus. Furthermore, they found that this increased risk for mortality was alleviated in patients who had a delay of HSCT after detecting RV in pre-transplant screening.21 Multiple retrospective studies focusing on more adult HSCT patients found associations between pre-transplant RVI and increased mortality and hospitalization, especially with increased risk for post-transplant complications such as myeloablative conditioning and symptomatic case.14, 15
A novel finding of this study is the relationship found between pre-transplant RVI and the requirement for ICU transfer post-HSCT. This correlation helps further the argument for the delay of transplant in lieu of a positive RV PCR result. ICU transfer is associated with substantial expenses, such as for invasive procedures and treatments taking place in the ICU, and the burden of heightened patient load for hospitals. The average overall cost for a stay in the pediatric intensive care unit (PICU) is approximately $15,000.19 Patients could benefit from the delay of transplant for non-malignant patients. This push for a delay of transplant is more significant given the increase in non-malignant conditions as indication for pediatric BMTs, Sickle Cell Anemia and Beta Thalassemia for example. As these conditions do not face an imminent risk of death, transplants for these patients could benefit from delay to avoid the potentially increased morbidity and mortality from HSCT.
This study corroborates associations between pre-transplant RVI and mortality and morbidity (in the form of requirement for ICU transfer), but limitations should be acknowledged before accepting this correlation. One, this study is retrospective, so delays in transplants were made on a case-by-case basis and not according to a proposed guideline. Due to its subjective nature, the reliability of the benefit of delay of transplant in the situation of a positive RVI PCR test result is limited. As this was a single center study it is possible that thresholds for transfer to ICU may vary which may impact generalizability. Although we sought to evaluate differences between asymptomatic and symptomatic patients, the too-small number of cases of symptomatic disease forced us to join the two groups in statistical analyses. Despite these shortcomings, the study was systematic and part of a standard operating procedure (SOP).
More research needs to be done to compare how symptomatic and asymptomatic RVI differ in their increased risk for post-transplant mortality and morbidity. While the delay of transplant may be effective at reducing complications in the setting of pre-transplant RV detection, a delay affordable for HSCTS for non-malignant disease, the extent of this benefit needs to be determined. This is important in cases of a malignant indications for transplant in which a delay in transplant may pose a more severe risk than the complications conferred by pre-transplant RVI. Delay of transplant may also necessitate the cryopreservation of donor, which have been associated with worse outcomes in cases such as severe aplastic anemia (SAA), or the loss of a match unrelated donor. Future studies would ideally be multi-center and prospective.