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

Courtney M. Rowan, Lincoln Smith, Matthew P. Sharron, Laura Loftis, Sapna Kudchadkar, Christine N. Duncan, Francis Pike, Paul A. Carpenter, David Jacobsohn, Catherine M. Bollard, Conrad Russell Y. Cruz, Abhijeet Malatpure, Sherif Farag, Jamie Renbarger, Morgan R. Little, Phillip R. Gafken, Robert A. Krance, Kenneth R. Cooke, Sophie Paczesny

Research output: Contribution to journalArticlepeer-review

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 5 213) and validation (n 5 119) 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.

Original languageEnglish (US)
Pages (from-to)1866-1878
Number of pages13
JournalBlood Advances
Volume6
Issue number6
DOIs
StatePublished - Mar 22 2022

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation'. Together they form a unique fingerprint.

Cite this