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.