Pathogen Identification in Pediatric Hematopoietic Stem Cell Transplant Patients With Suspected Lower Respiratory Tract Infection

This study is a multicenter cross-sectional observational analysis of unused lower
respiratory tract secretions collected from children with a history of HCT who are undergoing
evaluation for pulmonary complications. Patients will be screened and enrolled by study
coordinators at each site, who will collect and submit biospecimens as well as patient
characteristics and clinical outcomes. Metagenomic NGS will be performed on these
biospecimens in an attempt to identify microbial pathogens and markers of host response to
infection, including immune activation, inflammation, and cell damage. This study will then
correlate these results with patient characteristics, clinical microbiology test results, and
clinical outcomes in order to evaluate the utility of metagenomics NGS in improving the
diagnosis of LRTI in our pediatric HCT population.

Inclusion Criteria:

- Patients will be ≤21 years of age with a history of HCT of any type at any point in
the past, and are planned to undergo clinically-indicated collection of any lower
respiratory specimen, including but not limited to bronchoalveolar lavage (either via
a plugged telescoping catheter such as a CombiCath, or with fiberoptic bronchoscopy)
and tracheal aspirate.

- For the purposes of this study, induced or spontaneous sputum is not considered a
lower respiratory tract specimen.

- Patients may have any underlying indication for clinical testing of lower respiratory
secretions, including but not limited to suspected infection, non-infectious
inflammation, obstructive or restrictive lung disease, pulmonary edema, pleural
effusions, alveolar hemorrhage, aspiration, or pulmonary vascular disease.

- Patients who have not undergone HCT but plan to undergo HCT in the future, hereafter
referred to as pre-HCT patients, may also be enrolled.

- Pre-HCT patients must have intention to undergo stem cell transplantation in the
future and include but are not limited to patients with primary immunodeficiency,
patients with malignancy undergoing induction or consolidation chemotherapy, and HCT
patients with selected cell sources who are undergoing pre-transplant conditioning but
have not yet received their cellular infusion.

Exclusion Criteria:

- Patients will not be >21 years of age.

- Patients who do not have a clinical indication for obtaining lower respiratory
secretions for testing as part of their direct patient care will be excluded.

- Patients who do not have sufficient respiratory secretions remaining after collection
and aliquoting for indicated clinical tests ordered by the treating clinician will
also be excluded.

- Patients who undergo lower respiratory testing solely to evaluate for relapsed
malignancy will be excluded.