Predictive Value of Clinical Findings and Plasma Biomarkers after Fourteen Days of Prednisone Treatment for Acute Graft-versus-host Disease

McDonald, George B.; Tabellini, Laura; Storer, Barry E.; Martin, Paul J.; Lawler, Richard L.; Rosinski, Steven L.; Schoch, H. Gary

doi:10.1016/j.bbmt.2017.04.029

Cited by 29 publications

(21 citation statements)

References 43 publications

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“…High ST2 and Regenerating islet-derived 3-α (REG3α) when monitored as early as 1 week after the initiation of treatment determined the non-responder rates (64). Similar findings were reported with the combination of ST2 and T-cell immunoglobulin mucin-3 (TIM3) at 14 days post initiation of prednisone (64,65).…”

Section: Systemic Biomarkerssupporting

confidence: 57%

Biomarkers for Allogeneic HCT Outcomes

et al. 2020

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Allogeneic hematopoietic cell transplantation (HCT) remains the only curative therapy for many hematological malignant and non-malignant disorders. However, key obstacles to the success of HCT include graft-versus-host disease (GVHD) and disease relapse due to absence of graft-versus-tumor (GVT) effect. Over the last decade, advances in "omics" technologies and systems biology analysis, have allowed for the discovery and validation of blood biomarkers that can be used as diagnostic test and prognostic test (that risk-stratify patients before disease occurrence) for acute and chronic GVHD and recently GVT. There are also predictive biomarkers that categorize patients based on their likely to respond to therapy. Newer mathematical analysis such as machine learning is able to identify different predictors of GVHD using clinical characteristics pre-transplant and possibly in the future combined with other biomarkers. Biomarkers are not only useful to identify patients with higher risk of disease progression, but also help guide treatment decisions and/or provide a basis for specific therapeutic interventions. This review summarizes biomarkers definition, omics technologies, acute, chronic GVHD and GVT biomarkers currently used in clinic or with potential as targets for existing or new drugs focusing on novel published work.

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Section: Systemic Biomarkerssupporting

confidence: 57%

Biomarkers for Allogeneic HCT Outcomes

et al. 2020

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“…53 However, the majority of the other biomarkers discovered so far do correlate with clinical data; or (2) response to treatment, 53,67,[69][70][71] but can also be used as potential response measures to adapt the treatment. 98 Currently, there are no "preemptive intervention" clinical trials using biomarkers measured prior to clinical manifestation of GVHD. Although a schema for a preemptive trial to decrease the aGVHD incidence using biomarkers has been reported, 96,97 cGVHD biomarkers still lack the sensitivity and specificity required for clinical trial use.…”

Section: Incorporating Posttransplantation Biomarkers In Clinical Trialsmentioning

confidence: 99%

Biomarkers for posttransplantation outcomes

Paczesny

2018

Blood

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During the last decade, the development of biomarkers for the complications seen after allogeneic hematopoietic stem cell transplantation has expanded tremendously, with the most progress having been made for acute graft-versus-host disease (aGVHD), a common and often fatal complication. Although many factors are known to determine transplant outcome (including the age of the recipient, comorbidity, conditioning intensity, donor source, donor-recipient HLA compatibility, conditioning regimen, posttransplant GVHD prophylaxis), they are incomplete guides for predicting outcomes. Thanks to the advances in genomics, transcriptomics, proteomics, and cytomics technologies, blood biomarkers have been identified and validated for us in promising diagnostic tests, prognostic tests stratifying for future occurrence of aGVHD, and predictive tests for responsiveness to GVHD therapy and nonrelapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention. However, such blood tests are not yet available for routine clinical care. This article provides an overview of the candidate biomarkers for clinical evaluation and outlines a path from biomarker discovery to first clinical correlation, to validation in independent cohorts, to a biomarker-based clinical trial, and finally to general clinical application. This article focuses on biomarkers discovered with a large-scale proteomics platform and validated with the same reproducible assay in at least 2 independent cohorts with sufficient sample size according to the 2014 National Institutes of Health consensus on biomarker criteria, as well as on biomarkers as tests for risk stratification of outcomes, but not on their pathophysiologic contributions, which have been reviewed recently.

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“…38,39 A link between endothelial injury and GVHD is supported by a number of recent studies. [40][41][42][43][44] The ability to predict response to GVHD therapy using suppressor of tumorigenicity 2 (ST2) as a biomarker has been reproducibly demonstrated. 22,23 In addition, a connection between endothelial injury and release of soluble ST2 has been proposed and is supported by evidence from other inflammatory states like systemic scleroderma and chronic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Complement-mediated thrombotic microangiopathy as a link between endothelial damage and steroid-refractory GVHD

Wall¹,

Zhao²,

Yearsley³

et al. 2018

Blood Advances

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Transplant-associated thrombotic microangiopathy (TA-TMA), a complication of hematopoietic cell transplant (HCT), is associated with significant morbidity and mortality. The pathophysiology and overlap of TA-TMA with other posttransplant complications such as graft-versus-host disease (GVHD) is poorly understood. We retrospectively identified cases of TA-TMA among patients with grade 3/4 gastrointestinal (GI) GVHD, reviewed intestinal biopsy specimens, and performed correlative testing of biomarkers associated with TA-TMA. TA-TMA was more common in patients with steroid-refractory GVHD compared with steroid-responsive GVHD (79.3% vs 42.1%; P = .001). Among patients surviving 100 days post-HCT, 1-year survival from day 100 was significantly better for patients who had not developed TA-TMA in the first 100 days (69.5% vs 36.7%; P < .001). Only 1 of 7 proposed TA-TMA histology criteria (mucosal hemorrhage) differed significantly based on GVHD steroid response. In multivariable modeling, steroid-refractory GVHD was a risk factor for development of TA-TMA (hazard ratio, 3.09; 95% confidence interval, 1.68-5.67; P < .001). There were no differences in complement activation at GVHD onset; however, 2 to 6 weeks later, patients with TA-TMA had higher levels of BBPlus and C5b-9, markers of alternative and terminal pathway activation (BBPlus: median, 600 vs 209.3 ng/mL; P = .0045) (C5b-9: median, 425.9 vs 258.4 ng/mL; P = .029). TA-TMA is associated with poor overall survival (OS) following HCT and may be detected early by histologic findings and may be differentiated from GVHD by measurement of alternative and terminal complement pathway activation. It is unknown whether treatment of TA-TMA will improve survival in steroid-refractory GVHD.

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Predictive Value of Clinical Findings and Plasma Biomarkers after Fourteen Days of Prednisone Treatment for Acute Graft-versus-host Disease

Cited by 29 publications

References 43 publications

Biomarkers for Allogeneic HCT Outcomes

Biomarkers for Allogeneic HCT Outcomes

Biomarkers for posttransplantation outcomes

Complement-mediated thrombotic microangiopathy as a link between endothelial damage and steroid-refractory GVHD

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