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).