(1196) Correlation of Blood and BAL Transcriptomes in Lung Injury After Pediatric Stem Cell Transplant

Sunday, February 23, 2025

11:00am – 12:00pm Eastern Time

Location: Connections Central - RST 16

First Author(s)

EP

Emma M. Pearce, BS

Research Associate
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, United States

Co-Author(s)

Erica M. Evans, MD (she/her/hers)

University of California San Francisco Medical Center, USA
MM

Madeline Y. Mayday, BS

Graduate Student
Departments of Laboratory Medicine and Pathology, Yale School of Medicine, United States
GR

Gustavo Reyes, BA

Research Associate
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, United States
MS

Miriam R. Simon, BA

Medical Student
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, United States
JB

Jacob R. Blum, n/a

Undergraduate Student
Tufts University, United States
HK

Hanna Kim, BA

Research Associate
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, United States
CD

Christopher C. Dvorak, MD

Professor, Pediatric Bone Marrow Transplant
Division of Allergy, Immunology, and Bone Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, United States
JD

Joseph L. DeRisi, PhD

Professor, Biochemistry & Biophysics
Department of Biochemistry and Biophysics, University of California, San Francisco, United States
MZ

Matt S. Zinter, MD

Associate Professor, Pediatric Critical Care Medicine
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, United States

Introduction: More than 12,000 children with hematopoietic disorders have undergone hematopoietic stem cell transplants (HCTs) in the United States between 2016 and 2020. Up to 40% of these patients develop pulmonary injury and 20% require intensive care resulting from HCT toxicity. We previously showed that bronchoalveolar lavage (BAL) transcriptomes form 4 clusters that can characterize post-HCT pulmonary injury and predict outcomes. This research aims to define the relationship between blood and BAL transcriptomes.

Methods: We used 220 paired BAL and blood samples from 175 pediatric HCT patients enrolled at 32 children’s hospitals between 2014 and 2022. Samples underwent RNA sequencing and protein-coding genes were analyzed for differential expression. BAL-blood transcriptome correlation was assessed using gene-gene Spearman correlation. Blood gene expression variation across previously-identified patient clusters was explored using ANOVA-like models and significant genes were used in random forest classifier of cluster assignment. Finally, blood transcriptomes were compared by patient survival outcome.

Results: Most protein-coding genes varied in expression between sites (n=17,978 DEGs, FDR < 0.05). However, the median gene-wise Spearman correlation coefficient was -0.025 (IQR -0.081 to +0.030) across body sites. Enrichment scores of MSigDB Hallmark gene sets were also poorly correlated (median 0.036, IQR -0.037 to +0.133). An ANOVA-like approach identified 4,110 genes whose blood levels differed by BAL cluster assignment. However, a random forest classifier using blood transcripts showed moderate accuracy in assigning BAL clusters (accuracy 0.629, 95% CI 0.571-0.664). Finally, in-hospital mortality was associated with blood expression levels of 412 genes enriched for MSigDB Hallmark Hypoxia and Epithelial-Mesenchymal Transition pathways (p < 0.05).

Conclusions: Across 220 pediatric HCT patients with lung injury, we identified minimal BAL-blood transcriptome correlation, suggesting body site compartmentalization of injury response. However, a unique blood signature-associated outcome was detected independent of the previously identified pulmonary signatures, expanding our understanding of the systemic processes involved in post-HCT lung injury.