Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

Santosh Putta; Bradford A. Young; John E. Levine; Ran Reshef; Ryotaro Nakamura; Christopher Strouse; Miguel-Angel Perales; Alan Howard; Polly Pine; Ju Shi; Peixin Zhang; Vincent T. Ho; Wael Saber

doi:10.1016/j.jtct.2022.11.024

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Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

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Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

Santosh Putta, Bradford A. Young, John E. Levine, Ran Reshef, Ryotaro Nakamura, Christopher Strouse, Miguel-Angel Perales, Alan Howard, Polly Pine, Ju Shi, …

Transplantation and cellular therapy, Vol.29(3), pp.166.e1-166.e10

03/2023

DOI: 10.1016/j.jtct.2022.11.024

PMCID: PMC10116945

PMID: 36574581

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Abstract

•Plasma biomarkers are prognostic of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) risk post-hematopoietic cell transplantation (HCT) before clinical symptoms manifest.•Plasma biomarkers are prognostic of VOD/SOS by 7 days post-HCT.•Plasma biomarkers are prognostic of disease risk independent of risk factors.•Future validation with independent datasets may guide earlier clinical intervention. Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). This study aimed to determine a blood biomarker signature early post-HCT that identifies patients at high risk for VOD/SOS. A set of 23 plasma biomarkers, selected from the VOD/SOS literature, was measured on days 0, 7, and 14 after myeloablative HCT using blood samples from patients enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1202. Eligible cases were diagnosed with VOD/SOS in BMT CTN 1202 using the Baltimore criteria. Controls (without VOD/SOS) were matched to cases for conditioning regimen and age. Significant biomarkers were identified using the Bonferroni-adjusted Wilcoxon rank-sum test (P ≤ .002). Thirty-three patients with mild or severe VOD/SOS were identified (cases) and matched to 107 controls. Two, 8, and 5 biomarkers measured from the plasma of these patients were significantly associated with the development of VOD/SOS at days 0, 7, and 14, respectively, with the strongest associations on days 7 and 14. Biomarker associations were stronger for severe VOD/SOS risk and were stronger prognostic markers for VOD/SOS cases occurring within 28 days of HCT. Hyaluronan was most strongly associated with VOD/SOS risk, with an area under the receiver operating characteristic curve (AUC) of .81 on day 7 and .79 on day 14. Multivariate models of up to 5 biomarkers generated AUCs ranging from .82 to .85. All associations with VOD/SOS risk were independent of clinical risk factors. This study confirms previously identified biomarkers of VOD/SOS risk and identified novel prognostic biomarker signatures that identify patients at risk for VOD/SOS shortly after HCT. Multivariate analysis suggests that a combination of up to 5 of these protein biomarkers may provide a prognostic tool for identifying patients at risk for VOD/SOS.

Biomarkers

Defibrotide

Sinusoidal obstruction syndrome

Veno-occlusive disease

Details

Title: Subtitle: Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study
Creators: Santosh Putta - BioLegend (United States)
Bradford A. Young - Biotech (Brazil)
John E. Levine - Icahn School of Medicine at Mount Sinai
Ran Reshef - Columbia University
Ryotaro Nakamura - City Of Hope National Medical Center
Christopher Strouse - University of Iowa
Miguel-Angel Perales - Memorial Sloan Kettering Cancer Center
Alan Howard - Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota
Polly Pine - Jazz Pharmaceuticals, Palo Alto, California
Ju Shi - Jazz Pharmaceuticals, Palo Alto, California
Peixin Zhang - Jazz Pharmaceuticals, Palo Alto, California
Vincent T. Ho - Dana-Farber Cancer Institute
Wael Saber - Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin
Resource Type: Journal article
Publication Details: Transplantation and cellular therapy, Vol.29(3), pp.166.e1-166.e10
DOI: 10.1016/j.jtct.2022.11.024
PMID: 36574581
PMCID: PMC10116945
NLM abbreviation: Transplant Cell Ther
ISSN: 2666-6367
eISSN: 2666-6367
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute; DOI: 10.13039/100000054, name: National Cancer Institute; DOI: 10.13039/100011096, name: Jazz Pharmaceuticals, award: U10HL069294, U24HL138660
Language: English
Electronic publication date: 11/28/2022
Date published: 03/2023
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984363433002771

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