TY - JOUR
T1 - A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation
AU - Rowan, Courtney M.
AU - Smith, Lincoln
AU - Sharron, Matthew P.
AU - Loftis, Laura
AU - Kudchadkar, Sapna
AU - Duncan, Christine N.
AU - Pike, Francis
AU - Carpenter, Paul A.
AU - Jacobsohn, David
AU - Bollard, Catherine M.
AU - Cruz, Conrad Russell Y.
AU - Malatpure, Abhijeet
AU - Farag, Sherif
AU - Renbarger, Jamie
AU - Little, Morgan R.
AU - Gafken, Phillip R.
AU - Krance, Robert A.
AU - Cooke, Kenneth R.
AU - Paczesny, Sophie
N1 - Publisher Copyright:
© 2022 American Society of Hematology. All rights reserved.
PY - 2022/3/22
Y1 - 2022/3/22
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2021005770
DO - 10.1182/bloodadvances.2021005770
M3 - Article
C2 - 35139145
AN - SCOPUS:85127277945
SN - 2473-9529
VL - 6
SP - 1866
EP - 1878
JO - Blood Advances
JF - Blood Advances
IS - 6
ER -