EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis

Luft, Thomas; Benner, Axel; Jodele, Sonata; Dandoy, Christopher E.; Storb, Rainer; Gooley, Ted; Sandmaier, Brenda M.; Becker, Natália; Radujkovic, Aleksandar; Dreger, Peter; Penack, Olaf

doi:10.1016/s2352-3026(17)30108-4

Cited by 107 publications

(116 citation statements)

References 35 publications

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“…91,92 Routine laboratory measurements (lactate dehydrogenase, creatinine, and thrombocytes) can be used to create a formula called the Endothelial Activation and Stress Index (EASIX), which was found as a predictor of survival in patients with reduced-intensity conditioning. 93…”

Section: Hepatic Sosmentioning

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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Section: Hepatic Sosmentioning

confidence: 99%

Biomarkers for posttransplantation outcomes

Paczesny

2018

Blood

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“…This endothelial vulnerability has been mechanistically associated with multiple serious post- HCT complications, and clinical FO may represent another such toxicity. 24–26 …”

Section: Discussionmentioning

confidence: 99%

Early Fluid Overload Is Associated with an Increased Risk of Nonrelapse Mortality after Ex Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation

Rondon-Clavo

Scordo

Hilden

et al. 2018

Biology of Blood and Marrow Transplantation

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In a recently published and validated definition of fluid overload (FO), grade ≥ 2 FO was significantly associated with an increased risk of nonrelapse mortality (NRM) after unmodified and haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis. We evaluated the effect of FO on outcomes in 169 patients undergoing myeloablative-conditioned ex vivo CD34 selected allo-HCT using the same grading scale. Thirty patients (17.8%) had grade ≥ 2 FO within the 30 days after ex vivo CD34 selected allo-HCT with a median onset at day 11 (range, -8 to 28). Age ≥ 55 years (odds ratio, 3.43; P = .005) and chemotherapy-based conditioning (odds ratio, 3.89; P = .007) were associated with an increased risk of grade ≥ 2 FO. Patients with early grade ≥ 2 FO had a significantly higher NRM when compared with patients with grade < 2 FO (24.1% versus 3.6% at day 100, P = .01). The HCT-specific comorbidity index (HCT-CI) ≥ 3, FEV < 80, adjusted DL < 80, and HLA mismatch were associated with an increased risk of NRM, whereas total body irradiation-based conditioning was associated with a reduced risk of NRM. In a multivariate analysis grade ≥ 2 FO was associated with increased NRM after adjusting for HCT-CI and HLA match (hazard ratio, 2.3; P = .014). There was a trend toward inferior relapse-free survival in patients with grade ≥ 2 FO compared with patients with grade < 2 FO, 62% versus 72% at 1 year (P = .07), and a trend toward inferior overall survival, 69% versus 79% at 1 year (P = 0.06), respectively. Our findings show that FO should be routinely assessed to identify patients at risk for NRM. Despite a CNI-free allo-HCT platform, regimen-related tissue and endothelial injury leads to FO in susceptible patients. FO is a highly relevant post-HCT toxicity that requires further inquiry.

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“…The present article found that the analysis of these serum markers is simple and inexpensive method so, they might be employed to accelerate GVHD diagnosis. Further, these markers might have a postulated role in the pathophysiology of GVHD 14 .…”

Section: Application Of Latent Class Analysis In Diagnosis Of Graft-vmentioning

confidence: 99%

Application of latent class analysis in diagnosis of graft-versus-host disease by serum markers after allogeneic haematopoietic stem cell transplantation

Amini

Kazemnejad

Rasekhi

et al. 2020

Sci Rep

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2 for a composite test is as the same as a diagnostic test. For choosing optimal cutoff point, the Youden index which mentioned before, was used for the combinations. Afterward, the cSensitivity and cSpecificity were selected. For the models, the convergence of the MCMC chains for all the LCMs (with and without covariate adjustment) was assessed using autocorrelation plots. Furthermore, the convergence was obtained by running one chain with 35,000 iterations with lag 45. The first 17,000 iterations were discarded. The Bayesian latent class models were fitted by using OpenBUGS 3.2.1 41. The R package R2OpenBUGS 42 also applied as an interface between R 3.6.2 43 and OpenBUGS. After determining the GVHD groups based on optimal composite test, in order to evaluate the association between each of continuous variables and GVHD, an independent sample t-test was performed and chi-square test was applied for each categorical variable. All comparisons were two-tailed and p-value of less than 0.05 was taken as statistically significant. Descriptive analyses were performed using R version 3.6.2.

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EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis

Cited by 107 publications

References 35 publications

Biomarkers for posttransplantation outcomes

Biomarkers for posttransplantation outcomes

Early Fluid Overload Is Associated with an Increased Risk of Nonrelapse Mortality after Ex Vivo CD34-Selected Allogeneic Hematopoietic Cell Transplantation

Application of latent class analysis in diagnosis of graft-versus-host disease by serum markers after allogeneic haematopoietic stem cell transplantation

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