Elevated REG3α predicts refractory aGVHD in patients who received steroids-ruxolitinib as first-line therapy

Yang, Jingjing; Peng, Bo; Wang, Lu; Li, Xin; Li, Fēi; Jin, Xiangshu; Jia, Mingyu; Xu, Lei; Dou, Liping; Liu, Dai‐Hong

doi:10.1007/s00277-021-04727-1

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…The MAP score has been shown to be helpful when measured at day 28 along with the disease risk index could also identify patients at high relapse risk and low non-relapse mortality risk who can potentially benefit from strategies to enhance the graft versus leukemia effect for relapse prevention ( 63 ). Rising REG3α following treatment for GVHD using a novel combination of upfront steroids+ruxolitinib was shown to be a predictor of refractory GVHD ( 64 ). However, there is no prospective clinical study on biomarker-based intervention for adding second-line therapy for acute GVHD.…”

Section: Biomarkers For Acute Gvhdmentioning

confidence: 99%

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

Balakrishnan

Kulkarni²,

Pai³

et al. 2023

Front. Immunol.

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Hematopoietic cell transplantation is an established curative treatment option for various hematological malignant, and non-malignant diseases. However, the success of HCT is still limited by life-threatening early complications post-HCT, such as Graft Versus Host Disease (GVHD), Sinusoidal Obstruction Syndrome (SOS), and transplant-associated microangiopathy, to name a few. A decade of research in the discovery and validation of novel blood-based biomarkers aims to manage these early complications by using them for diagnosis or prognosis. Advances in this field have also led to predictive biomarkers to identify patients’ likelihood of response to therapy. Although biomarkers have been extensively evaluated for different complications, these are yet to be used in routine clinical practice. This review provides a detailed summary of various biomarkers for individual early complications post-HCT, their discovery, validation, ongoing clinical trials, and their limitations. Furthermore, this review also provides insights into the biology of biomarkers and the challenge of obtaining a universal cut-off value for biomarkers.

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Section: Biomarkers For Acute Gvhdmentioning

confidence: 99%

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

Balakrishnan

Kulkarni²,

Pai³

et al. 2023

Front. Immunol.

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“…We previously reported that steroids‐ruxolitinib as the first‐line treatment for intermediate‐to high‐risk aGVHD resulted in an 82.05% complete remission (CR) rate at day 28. But 18.8% of these patients who achieved CR ( n = 32) subsequently developed RaGVHD 9 . A randomized trial supported that sirolimus as initial therapy for standard‐risk aGVHD provided similar day 28 response rates as steroids.…”

Section: Introductionmentioning

confidence: 99%

“…But 18.8% of these patients who achieved CR (n = 32) subsequently developed RaGVHD. 9 A randomized trial supported that sirolimus as initial therapy for standard-risk aGVHD provided similar day 28 response rates as steroids. However, in the sirolimus group, aGHVD persistence/flare were seen before day 56 in 11.4% (4/35) patients with preceding CR/partial response (PR).…”

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confidence: 99%

Increased risk of nonrelapse mortality post T‐cell‐replete haploidentical stem cell transplantation in patients with recurrence of acute graft‐versus‐host disease

Peng

Dou

Yang

et al. 2022

Hematological Oncology

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Acute graft-versus-host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T-cellreplete haploidentical hematopoietic cell transplantation (haplo-HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo-HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1-year cumulative incidence of 19.0% (95% CI: 14.5-24.6). Grade III-IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD-related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse-free survival (HR: 1.9, p = 0.020) and cGVHD relapse-free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently.

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Recent advances in acute gastrointestinal graft versus host disease (aGvHD): aspects of steroid-resistant disease

Kujawska,

Zeiser,

Gil

2024

Ann Hematol

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Acute Graft versus Host Disease (aGvHD) is a common immunological complication occurring in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Moreover, aGvHD is associated with a higher risk of infections and metabolic complications, affecting non-relapse mortality. Progress in transplantation has changed the prophylactic and therapeutic strategies of aGvHD and improved patient outcomes. The standard first-line therapy remains steroids, with a response rate of about 50%. The Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, is an effective second-line therapy. The management of patients who developed a disease that is refractory to steroids and ruxolitinib, especially in the severe gastrointestinal forms of aGvHD, is not validated and remains an unmet medical need. In the article, we present the current clinical practice, as well as the latest advances targeting pathophysiological pathways of GvHD and gut microbiota, which may be a potential future of aGvHD therapy.

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Elevated REG3α predicts refractory aGVHD in patients who received steroids-ruxolitinib as first-line therapy

Cited by 4 publications

References 33 publications

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

Increased risk of nonrelapse mortality post T‐cell‐replete haploidentical stem cell transplantation in patients with recurrence of acute graft‐versus‐host disease

Recent advances in acute gastrointestinal graft versus host disease (aGvHD): aspects of steroid-resistant disease

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