Abstract:
Background: Hematopoietic Stem Cell Transplant (HSCT) is a
curative procedure for many life-threatening hematological indications.
Respiratory viral infections (RVI) cause substantial morbidity and
mortality in pediatric transplant recipients, but the impact of
mild/asymptomatic RVI is unclear. Some studies have identified certain
viral infections as high-risk for post-transplant complications. To
reduce transplant morbidity, a pre-transplant RVI screening program was
started at Children\RL’s National Hospital which included symptom
screening and respiratory viral (RV) PCR testing for each HSCT patient
within one week of and on the day of HSCT admission. The objective of
this study was to evaluate the impact of RVI on HSCT outcomes.
Methods: A retrospective review of pre-transplant RV PCR,
symptom screening, and clinical outcomes was done for patients receiving
allogeneic HSCT from 7/1/2016 to 3/31/2023. Exclusion criteria included
missing pre-transplant RV PCR and SCID to prevent bias.
Results: 161 patients were eligible to be included. Of the 161,
34 tested positive for RVs (26 low-risk, 8 high-risk). Outcomes were
initially analyzed separately by low- and high-risk viruses. Within the
first 100 days post-transplant, a positive pre-HSCT RVI was
significantly associated with increased mortality (odds ratio (OR) =
5.57, p = 0.04 after adjusting for multiple testing) and requirement for
ICU transfer (OR = 3.45, p = 0.006).
Conclusions: Routine pre-transplant viral testing should be
performed to increase the safety of HSCTs. Pre-transplant viral testing
may allow providers to know when to monitor certain patients more
closely post-transplant, and when to potentially delay elective
transplant until the patient has cleared their virus.
1 | Introduction :
Hematopoietic Stem Cell Transplant (HSCT) is a curative procedure for
many pediatric patients with life-threatening hematological conditions.
These patients are at a high risk for post-transplant complications,
including secondary infections, respiratory collapse, and even
death.1 This risk is heightened when the transplant is
performed in the setting of a respiratory viral infection (RVI),
especially in patients who have received myelosuppression, lymphopenia,
T-cell therapy, and immunosuppressive regimens.2-7When presented with positive RVI testing before an HSCT, multiple
factors must be considered in the decision to proceed or delay the
transplant. These factors include the condition of the patient, the
indication for transplant, associated symptoms, and the specific virus
or viruses at hand. The underlying condition necessitating transplant
might be aggressive and malignant, in which case delay of transplant
despite the presence of an RVI can be seen as more deleterious. Some
RVIs have a higher likelihood of causing post-transplant complications,
including adenovirus, human metapneumovirus (HMPV), influenza,
parainfluenza, and respiratory syncytial virus (RSV).4,
13, 14 Based on past studies, current clinical guidelines recommend
delaying transplant if a patient tests positive for one of these
viruses. There is no official stance on the decision to proceed with or
delay transplant in the case of lower-risk viruses, coronaviruses, and
human rhinoviruses (HRV).22, 23 Additionally, the
availability of the donor and product must be considered in
decision-making.
Past experimental studies purport inconsistent data on the effects of
pre-transplant RVI of different types on the complications
post-transplant. One past study performed in an adult population found
that symptomatic patients who tested positive for RVIs pre-HSCT had
fewer days alive and out of the hospital at day 100
post-transplant.14 This trend was seen in all types of
RVI, including rhinovirus, the most common RVI seen as incurring the
least amount of risk for post-transplant complications. Notably, this
increase was not found in asymptomatic patients.14 In
contrast to this finding, a retrospective study performed in Geneva
concluded that RVI within a month leading up to allogeneic HSCT was not
associated with transplant-related mortality or
morbidity.16
There are far fewer data and information available concerning pediatric
patients alone. One purely pediatric study looking at RVI within 90 days
of HSCT found no significant difference in mortality between patients
with and without RVI pre-transplant. They did conclude, however, that
patients who tested positive for any RVI had notably fewer days alive
and out of the hospital as compared to patients who tested
negative.13 More information is needed to determine
the cause of prolonged hospitalization but unaffected mortality in
pediatric patients going into transplant with RVIs. Another
retrospective study of a pediatric population confirmed this pattern,
but could not draw the same conclusion of increased hospitalization and
viral infections pre-transplant in multivariable
models.17 A pediatric study did find that patients who
went into transplant positive for one or more RVIs had decreased
survival and increased transplant-related mortality, but that this risk
was diminished by the delay of transplant.18 Overall,
more information is needed to conclude the necessity of pre-transplant
viral screening, if transplant should be delayed in the case of positive
results, and whether the presentation of symptoms informs this decision,
especially in a pediatric population.
With knowledge of the possible increased risk for post-transplant
complications given RVI, a pre-transplant RVI screening program was
started at Children\RL’s National Hospital. This program included an
RV PCR test and symptom screening for each HSCT patient before and upon
admission. This screening program is done on all pre-HSCT patients,
despite many institutions not performing RV PCR testing on asymptomatic
patients outside of research protocols.
To evaluate the benefit of this pre-transplant testing, we performed a
retrospective study on all HSCT pediatric patients at the hospital since
the onset of the screening program. The objective of this study was to
both assess the impact of RVI on HSCT outcomes, and whether or not the
presence of symptoms affected the risk of post-transplant complications.
2 | Methods :
This retrospective review was approved by the Children’s National
institutional review board (IRB).