A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation

Courtney M. Rowan, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Lincoln Smith, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
Matthew P. Sharron, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences and Children's National Hospital, Washington, DC.
Laura Loftis, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston,TX.
Sapna Kudchadkar, Department of Anesthesiology and Critical Care Medicine.
Christine N. Duncan, Department of Pediatrics, Dana-Farber Boston Children's Hospital, Harvard University, Boston, MA.
Francis Pike, Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN.
Paul A. Carpenter, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
David Jacobsohn, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences and Children's National Hospital, Washington, DC.
Catherine M. Bollard, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences and Children's National Hospital, Washington, DC.
Conrad Russell Cruz, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences and Children's National Hospital, Washington, DC.
Abhijeet Malatpure, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Sherif Farag, Department of Medicine, Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
Jamie Renbarger, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Morgan R. Little, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Phillip R. Gafken, Proteomics and Metabolomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA.
Robert A. Krance, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston,TX.
Kenneth R. Cooke, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Sophie Paczesny, Department of Microbiology and Immunology, and.

Document Type

Journal Article

Publication Date

3-22-2022

Journal

Blood advances

Volume

6

Issue

6

DOI

10.1182/bloodadvances.2021005770

Abstract

Plasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF. Six candidate proteins, from this discovery cohort or identified in the literature, were measured by enzyme-linked immunosorbent assay in day-7 and day-14 post-HCT samples from the training (n = 213) and validation (n = 119) cohorts. Cox proportional-hazard analyses with biomarkers dichotomized by Youden's index, as well as landmark analyses to determine the association between biomarkers and RF, were performed. Of the 6 markers, Stimulation-2 (ST2), WAP 4-disulfide core domain protein 2 (WFDC2), interleukin-6 (IL-6), and tumor necrosis factor receptor 1 (TNFR1), measured at day 14 post-HCT, had the most significant association with an increased risk for RF in the training cohort (ST2: hazard ratio [HR], 4.5, P = .004; WFDC2: HR, 4.2, P = .010; IL-6: HR, 6.9, P < .001; and TFNR1: HR, 6.1, P < .001) and in the validation cohort (ST2: HR, 23.2, P = .013; WFDC2: HR, 18.2, P = .019; IL-6: HR, 12.2, P = .014; and TFNR1: HR, 16.1, P = .001) after adjusting for the conditioning regimen. Using cause-specific landmark analyses, including days 7 and 14, high plasma levels of ST2, WFDC2, IL-6, and TNFR1 were associated with an increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality from RF. ST2, WFDC2, IL-6 and TNFR1 levels measured early posttransplantation improve risk stratification for RF and its related mortality.

Department

Pediatrics

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