Associations between acute GVHD-related biomarkers and endothelial cell activation after allogeneic hematopoietic stem cell transplantation

Nomura, Shosaku; Ishii, Kazuyoshi; Fujita, Shinya; Nakaya, Aya; Satake, Atsushi; Ito, Tomoki

doi:10.1016/j.trim.2017.06.004

Cited by 30 publications

(27 citation statements)

References 46 publications

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“…We also found elevated levels in patients with grade II-IV aGVHD (difference not statistically significant). Consistent with our results, Nomura et al (28) reported higher levels of REG3α on day 14 in patients who developed aGVHD (affected organ not detailed). Despite these results, few studies have analyzed the predictive role of this biomarker, since most focus on its diagnostic role.…”

Section: Discussionsupporting

confidence: 93%

“…This raises the possibility of effect on NK cells as IL-33/ST2 axis augments NK cell production of IFN-γ in response to IL-12 (27). Some studies did not find a statistically significant association between these entities (23, 25), whereas others, consistent with our study, observed a correlation between ST2 levels and GVHD (16, 24, 28, 29). However, such studies were not fully comparable with ours, since none of them included patients with haplo-HSCT or used PTCy as GVHD prophylaxis.…”

Section: Discussionsupporting

confidence: 82%

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ST2 and REG3α as Predictive Biomarkers After Haploidentical Stem Cell Transplantation Using Post-transplantation High-Dose Cyclophosphamide

et al. 2019

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Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative procedure for several hematological malignancies. Haploidentical HSCT (haplo-HSCT) using high-dose post-transplantation cyclophosphamide (PTCy) makes transplantation possible for patients with no HLA-matched sibling donor. However, this treatment can cause complications, mainly infection, graft-vs.-host disease (GVHD), and conditioning-related toxicity. In recent years, different biomarkers in the form of tissue-specific proteins have been investigated; these may help us to predict complications of allo-HSCT. In this study we explored two such biomarkers, suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (REG3α), in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed. ST2 and REG3α levels at day +15 were not associated with post-transplant complications. ST2 levels at day +30 were higher in patients with grade II-IV acute GVHD, mainly those who received reduced intensity conditioning (RIC; median 2,503 vs. 1,830 ng/ml; p = 0.04). Of note, patients with higher plasma ST2 levels at day +30 also presented a higher incidence of non-relapse mortality (HR, 7.9; p = 0.004) and lower 2-year overall survival (25 vs. 44 months; p = 0.02) than patients with lower levels. Patients with REG3α levels higher than 1,989 pg/ml at day +30 presented a higher incidence of acute gastrointestinal GVHD in the whole cohort (HR, 8.37; p = 0.003) and in the RIC cohort (HR 6.59; p = 0.01). These data suggest that measurement of ST2 and REG3α might be useful for the prognosis and prediction of complications in patients undergoing haplo-HSCT with PTCy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 82%

ST2 and REG3α as Predictive Biomarkers After Haploidentical Stem Cell Transplantation Using Post-transplantation High-Dose Cyclophosphamide

et al. 2019

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“…Activated protein C (aPC) signaling using protease-activated receptor 2/3 (PAR 2 and 3) expanded Tregs and mitigated aGvHD in mice [246]. rTM depends on GPR15 to mitigate murine aGvHD [167], whereas human patients receiving rTM were shown to have lower CCL5 levels and aGvHD [247]. The case of GPR43 merits further discussion; it is a sensor of gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs).…”

Section: Resultsmentioning

confidence: 99%

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

Golay

Mlakar

et al. 2019

IJMS

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Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for several malignant and non-malignant diseases at the cost of serious treatment-related toxicities (TRTs). Recent research on extending the benefits of HSCT to more patients and indications has focused on limiting TRTs and improving immunological effects following proper mobilization and engraftment. Increasing numbers of studies report associations between HSCT outcomes and the expression or the manipulation of G protein-coupled receptors (GPCRs). This large family of cell surface receptors is involved in various human diseases. With ever-better knowledge of their crystal structures and signaling dynamics, GPCRs are already the targets for one third of the current therapeutic arsenal. The present paper assesses the current status of animal and human research on GPCRs in the context of selected HSCT outcomes via a systematized survey and analysis of the literature.

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“…Thus, rhTM may be effective against both DIC and other complications that develop following allo-HSCT. Nomura et al [23] revealed a significant decrease in HMGB1 and lower frequencies of aGVHD in allo-HSCT patients treated with rhTM.…”

Section: Discussionmentioning

confidence: 98%

Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2018

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The prognosis for patients who experience hemostatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. However, no report has investigated disseminated intravascular coagulation (DIC) caused by the complications of allo-HSCT without infection. Recombinant human soluble thrombomodulin (rhTM) was used to treat 12 episodes of DIC (n = 10; group 1) caused by allo-HSCT complications such as acute graft-versus-host disease (aGVHD) or thrombotic microangiopathy (TMA), and the clinical outcomes were compared with those of historical controls (n = 9; group 2) treated for DIC without rhTM. In group 1, the mean DIC score was significantly improved after using rhTM. Fibrinogen degeneration product (FDP), C-reactive protein (CRP), and the inflammatory cytokine high-mobility group box 1 (HMGB1) were also significantly decreased. Serial changes from the baseline values of platelet counts and levels of FDP were significantly better in group 1 than in group 2. The recovery rate from DIC was significantly higher in group 1 than in group 2. These findings suggest that rhTM is effective against both DIC and systemic inflammatory complications after allo-HSCT.

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Associations between acute GVHD-related biomarkers and endothelial cell activation after allogeneic hematopoietic stem cell transplantation

Abstract: Our findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.

Cited by 30 publications

References 46 publications

ST2 and REG3α as Predictive Biomarkers After Haploidentical Stem Cell Transplantation Using Post-transplantation High-Dose Cyclophosphamide

ST2 and REG3α as Predictive Biomarkers After Haploidentical Stem Cell Transplantation Using Post-transplantation High-Dose Cyclophosphamide

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell Transplantation

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