A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation
dc.contributor.author | Rowan, Courtney M. | |
dc.contributor.author | Smith, Lincoln | |
dc.contributor.author | Sharron, Matthew P. | |
dc.contributor.author | Loftis, Laura | |
dc.contributor.author | Kudchadkar, Sapna | |
dc.contributor.author | Duncan, Christine N. | |
dc.contributor.author | Pike, Francis | |
dc.contributor.author | Carpenter, Paul A. | |
dc.contributor.author | Jacobsohn, David | |
dc.contributor.author | Bollard, Catherine M. | |
dc.contributor.author | Cruz, Conrad Russell Y. | |
dc.contributor.author | Malatpure, Abhijeet | |
dc.contributor.author | Farag, Sherif | |
dc.contributor.author | Renbarger, Jamie | |
dc.contributor.author | Little, Morgan R. | |
dc.contributor.author | Gafken, Phillip R. | |
dc.contributor.author | Krance, Robert A. | |
dc.contributor.author | Cooke, Kenneth R. | |
dc.contributor.author | Paczesny, Sophie | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2023-05-16T15:56:43Z | |
dc.date.available | 2023-05-16T15:56:43Z | |
dc.date.issued | 2022 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Rowan CM, Smith L, Sharron MP, et al. A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation. Blood Adv. 2022;6(6):1866-1878. doi:10.1182/bloodadvances.2021005770 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/33022 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Society of Hematology | en_US |
dc.relation.isversionof | 10.1182/bloodadvances.2021005770 | en_US |
dc.relation.journal | Blood Advances | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Biomarkers | en_US |
dc.subject | Hematopoietic stem cell transplantation | en_US |
dc.subject | Proportional hazards models | en_US |
dc.subject | Respiratory insufficiency | en_US |
dc.subject | Transplantation conditioning | en_US |
dc.title | A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation | en_US |
dc.type | Article | en_US |