Guidelines Needed for Monitoring Pulmonary Complications After Pediatric HSCT

Several priority areas need to be examined in future research to improve the quality of clinical guidelines to address when and how to monitor pediatric hematopoietic stem cell transplant survivors.

Variation in practices for monitoring pulmonary health of pediatric hematopoietic stem cell transplant (HSCT) survivors exists due to the lack of standardized guidelines and differences in access to diagnostic resources.1

Findings come from a survey published in Cancer Reports and show that several priority areas are needed to be examined in future research in order to improve the quality of clinical guidelines to address when and how to monitor these patients in this high-risk population.

“This survey reveals variations in screening for pulmonary complications of HSCT among children. Uniform and effective screening among pediatric HSCT survivors may minimize the detrimental effects of late pulmonary complications and result in improved quality of life and survival. Further research is essential to determine the optimal screening protocol, including the role of new tests such as MBW,” wrote the study authors led by Shivanthan Shanthikumar, MD.

HSCT is an established treatment for patients with malignant and non-malignant conditions as well as pulmonary disease. Being able to accurately detect pulmonary complications early is a critical step in improving long term outcomes as pulmonary disease is a leading cause of late term morbidity and mortality. Current guidelines for the surveillance of pulmonary complications post-HSCT contain conflicting recommendations regarding which tests should be performed, the frequency of testing, and do not include recommendations for patients who are unable to complete pulmonary function tests.

Because of this, an electronic web-based survey of HSCT physicians and pediatric pulmonologists was conducted to determine the breadth of current practice in monitoring for pulmonary complications of pediatric HSCT.

Using publicly available data, a list of HSCT centers in the United States and Australasia was created and 1 HSCT physician and 1 pediatric pulmonologist from each center were invited to complete an electronic survey. This survey was conducted in research electronic data capture, (REDCap), which is a web-based application serving to capture data used in the study.

The survey consisted of 37 questions which were divided into 6 domains, including general demographics, standard follow up, pulmonary function testing, imaging, access to pediatric pulmonology, and invasive diagnostic testing. Because the data was non-normally distributed, investigators tested correlations using the Mann Whitney test, with P values <.05 considered significant. All statistical analyses were performed using GraphPad Prism, version 6.01.

A total of 115 participants were distributed the survey across 68 different HSCT centers on October 14, 2019. The survey was given to both a HSCT physician and pediatric pulmonologist at 47 centers, a HSCT physician only at 12 centers, and a pediatric pulmonologist only at 9 centers. By the end, 40 (34.8%) responses were received, all of which were complete and included in the analysis.

In terms of demographics, 33 of the 40 (82.5%) participants were from the United States, and 25 (62.5%) were pediatric pulmonologists. Every one of the respondents worked at centers which performed both allogenic and autologous HSCT and worked at centers that performed HSCT for oncological indications. Then, 36 of the 40 participants (90%) also performed them for immune deficiency/ immune dysregulation and 34 (80%) for hemoglobinopathy.

Most of the respondents (n = 27, 67.5%) reported that a protocol for assessing pulmonary complications of pediatric HSCT existed at their institution, but 20% (n = 8) reported no protocol existed. The remainder of participants were unsure if a protocol existed at their center. Pulmonologists and HSCT physicians generally answered the same to this question (64% vs 73.3%, P =.68). Exactly half of the participants felt their center adhered well or very well to their protocol (n = 20; 50%). However, there were 10 participants (25%) who reported it to be poor or average adherence. There was no difference in responses between pulmonologists and HSCT physicians (P =.56). Additionally, 17 participants (42.5%) said that the type of HSCT (autologous vs allogeneic) affected the surveillance protocol while 15 (37.5%) did not. More than half (n = 40, 57.5%) of respondents reported that the indication for HSCT did not affect surveillance protocol.

The most performed pulmonary function tests prior to HSCT were diffusing capacity of the lungs for carbon monoxide in 38 respondents (95%) and spirometry in 37 (92.5%). Most of the respondents (95%) reported routine post-HSCT pulmonary function tests and impulse oscillometry was reported as an additional test by 2 participants (5%) while fractional exhaled nitric oxide was reported by 1 (2.5%).

The frequency of post-HSCT pulmonary function tests were most performed every 3 months (n = 14, 35%) or 6 months (n= 12, 30%) in the first year post-HSCT, every 6 months (n = 13, 32.5%) or 12 months (n = 13, 32.5%) in the second year post-HSCT, and every 12 months (n = 21, 52.5%) thereafter. No significant differences between the responses of pulmonologists and HSCT physicians were reported at any of these time points.

For patients with known pulmonary complications, most of the centers performed pulmonary function tests every 3 months (n = 21, 52.5%). For patients with known GVHD, pulmonary function tests were also performed every 3 months (n = 18, 45%). Pulmonary function tests were interpreted by pediatric pulmonologists in all centers, but there were 3 (7.5%) respondents who reported that adult pulmonologists sometimes interpreted tests.

Other than pulmonary function tests, the most commonly performed test was a 6-minute walk test (n = 21, 52.5%). In patients under 5 years of age, the most common test was using clinical symptoms and signs in 34 participants (85%), and computed tomography in 21 patients (52.5%). Then, 6 of the respondents (15%) reported using conventional pulmonary function tests in this age group, while 1 (2.5%) used a 6MWT, and another 1 (2.5%) used oxygen saturations. Additionally, most respondents said that chest computed tomography scans were performed pre-HSCT (n = 21, 52.5%). Most reported that they were not routinely repeated post-HSCT (n = 26, 65%).

When assessing pediatric pulmonology, it was shown that all 15 of the HSCT physician respondents worked in a center with access to pediatric pulmonology. A relatively even distribution between respondents reporting no routine referral to pediatric pulmonology (n = 21, 52.5%) and a routine referral (n = 19, 47.5%) were demonstrated. There was also an even distribution of whether centers had a defined pulmonologist for this patient group with 21 (52.5%) having had a defined clinician, and 19 (47.5%) who did not. No significant relationship between the presence of a defined pulmonologist and whether centers had a protocol for monitoring for complications and reported adherence to the protocol were reported.

Every respondent was a part of a center with access to bronchoscopy. All had been involved in a patient who had undergone bronchoalveolar lavage. Additionally, almost all the respondents had previously cared for a patient with a lung biopsy (95%). In most cases, this was looking for both infection and non-infectious pathology (85%). A variety of biopsy techniques were used with the most common being a thoracoscopic biopsy in 29 participants (72.5%). Other types of biopsies included an open surgical biopsy (57.5%), transbronchial biopsy (25%), interventional radiology guided biopsy (20%), and endobronchial ultrasound guided biopsy (7.5%). The other 5% was not applicable.

“Simultaneous to this research there is a clear and urgent need for uniform clinical guidelines in this area, with consideration given to feasibility of implementation as broadly as possible, especially as it relates to unequal distribution of resources. This guidance could be derived from a rigorous systematic review of existing literature, led by an international group of HSCT physicians and pediatric pulmonologists. Such a guideline would likely reduce variation in care and lead to improved clinical outcomes for pediatric HSCT survivors,” added the study authors.

Shanthikumar S, Gower WA, Abts M, et al. Pulmonary surveillance in pediatric hematopoietic stem cell transplant: A multinational multidisciplinary survey. Cancer Rep (Hoboken). 2022;5(5):e1501. doi:10.1002/cnr2.1501