Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation
BACKGROUND Currently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-05-01
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| Series: | JCI Insight |
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| Online Access: | https://doi.org/10.1172/jci.insight.168221 |
| _version_ | 1797634266428866560 |
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| author | Yan Han Alan Bidgoli Brittany P. DePriest Alejandra Méndez Khadijeh Bijangi-Vishehsaraei Evelio D. Perez-Albuerne Robert A. Krance Jamie Renbarger Jodi L. Skiles Sung W. Choi Hao Liu Sophie Paczesny |
| author_facet | Yan Han Alan Bidgoli Brittany P. DePriest Alejandra Méndez Khadijeh Bijangi-Vishehsaraei Evelio D. Perez-Albuerne Robert A. Krance Jamie Renbarger Jodi L. Skiles Sung W. Choi Hao Liu Sophie Paczesny |
| author_sort | Yan Han |
| collection | DOAJ |
| description | BACKGROUND Currently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2). METHODS Between 2017 and 2021, we prospectively accrued 80 pediatric patients across 4 US centers. Biomarkers were tested by ELISA blind to patient groupings and associated with SOS incidence on day 35 after HCT, and overall survival (OS) on day 100 after HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort.RESULTS Combination of the 3 biomarkers measured on day 3 after HCT in the prospective cohort provided 80% (95% CI 55%–100%) sensitivity and 73% (95% CI 62%–83%) specificity for risk of SOS occurrence. Patients with low L-ficolin were 9 times (95% CI 3–32) more likely to develop SOS, while patients with high HA and ST2 were 6.5 (95% CI 1.9–22.0) and 5.5 (95% CI 2.3–13.1) times more likely to develop SOS. These 3 markers also predicted worse day 100 OS — L-ficolin: HR, 10.0 (95% CI 2.2–45.1), P = 0.0002; HA: HR, 4.1 (95% CI 1.0–16.4), P = 0.031; and ST2: HR, 3.9 (95% CI 0.9–16.4), P = 0.04.CONCLUSION L-ficolin, HA, and ST2 levels measured as early as 3 days after HCT improved risk stratification for SOS occurrence and OS and may guide risk-adapted preemptive therapy.TRIAL REGISTRATION ClinicalTrials.gov NCT03132337.FUNDING NIH. |
| first_indexed | 2024-03-11T12:05:17Z |
| format | Article |
| id | doaj.art-0bce86b94c4843e7b5dc401e30206d26 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:05:17Z |
| publishDate | 2023-05-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-0bce86b94c4843e7b5dc401e30206d262023-11-07T16:25:39ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-05-01810Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantationYan HanAlan BidgoliBrittany P. DePriestAlejandra MéndezKhadijeh Bijangi-VishehsaraeiEvelio D. Perez-AlbuerneRobert A. KranceJamie RenbargerJodi L. SkilesSung W. ChoiHao LiuSophie PaczesnyBACKGROUND Currently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2). METHODS Between 2017 and 2021, we prospectively accrued 80 pediatric patients across 4 US centers. Biomarkers were tested by ELISA blind to patient groupings and associated with SOS incidence on day 35 after HCT, and overall survival (OS) on day 100 after HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort.RESULTS Combination of the 3 biomarkers measured on day 3 after HCT in the prospective cohort provided 80% (95% CI 55%–100%) sensitivity and 73% (95% CI 62%–83%) specificity for risk of SOS occurrence. Patients with low L-ficolin were 9 times (95% CI 3–32) more likely to develop SOS, while patients with high HA and ST2 were 6.5 (95% CI 1.9–22.0) and 5.5 (95% CI 2.3–13.1) times more likely to develop SOS. These 3 markers also predicted worse day 100 OS — L-ficolin: HR, 10.0 (95% CI 2.2–45.1), P = 0.0002; HA: HR, 4.1 (95% CI 1.0–16.4), P = 0.031; and ST2: HR, 3.9 (95% CI 0.9–16.4), P = 0.04.CONCLUSION L-ficolin, HA, and ST2 levels measured as early as 3 days after HCT improved risk stratification for SOS occurrence and OS and may guide risk-adapted preemptive therapy.TRIAL REGISTRATION ClinicalTrials.gov NCT03132337.FUNDING NIH.https://doi.org/10.1172/jci.insight.168221OncologyTransplantation |
| spellingShingle | Yan Han Alan Bidgoli Brittany P. DePriest Alejandra Méndez Khadijeh Bijangi-Vishehsaraei Evelio D. Perez-Albuerne Robert A. Krance Jamie Renbarger Jodi L. Skiles Sung W. Choi Hao Liu Sophie Paczesny Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation JCI Insight Oncology Transplantation |
| title | Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| title_full | Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| title_fullStr | Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| title_full_unstemmed | Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| title_short | Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| title_sort | prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation |
| topic | Oncology Transplantation |
| url | https://doi.org/10.1172/jci.insight.168221 |
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