[Advances in pathogenesis and treatment of chronic graft resistance to persistent diseases]
Jing Yang1, Mengmeng Zhang1, Yajing Xu1
1Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China.
Insights
Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplants. New therapies targeting immune cells and fibrosis show promise beyond steroids for refractory cGVHD.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Chronic graft-versus-host disease (cGVHD) is a leading cause of non-relapse mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- cGVHD presents with multi-system involvement and fibrosis, mimicking autoimmune diseases.
- Current first-line glucocorticoid therapy has limitations due to severe complications and steroid resistance.
Purpose of the Study:
- To review emerging therapeutic strategies for cGVHD.
- To highlight novel approaches addressing the limitations of conventional treatments.
Main Methods:
- Literature review of clinical and preclinical studies on cGVHD treatments.
- Analysis of novel therapeutic targets including immune cell modulation and anti-fibrosis strategies.
Main Results:
- Various immunomodulatory approaches show promise, including T-cell and B-cell depletion strategies.
- Targeting B-cell receptor signaling and cytokine pathways offers new therapeutic avenues.
- Enhancing regulatory T cells (Tregs) and employing anti-fibrosis therapies are supported by preclinical and clinical data.
Conclusions:
- Novel therapeutic strategies beyond standard immunosuppression are emerging for cGVHD.
- Targeting specific immune pathways and fibrosis presents a promising future for managing refractory cGVHD.
- Further clinical investigation is warranted for these advanced treatment modalities.
Abstract:
Chronic graft-versus-host disease (cGVHD) is a major cause for late non-relapse-related death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and seriously affects their quality of life. cGVHD may involve many systems in the whole body and its clinical manifestations are similar to autoimmune diseases, and the main pathology is fibrosis. The therapeutic regimen based on glucocorticoids remains as the first-line treatment for cGVHD. Since long-term and high-dose application of glucocorticoids result in serious complications, along with the appearance of steroid-resistant and recurrence/refractory cGVHD, conventional immune suppressive agents have limited clinical efficacy. With the progress in understanding of the pathological mechanisms for cGVHD, many treatments, such as depletion of alloreactive T cells, B-cell depletion, preventing B cell differentiation, targeting the B-cell receptor signaling pathway, inhibition of cytokine receptor-mediated signaling, enhancement of Tregs in vivo, adoptive Tregs therapy, facilitating Tregs reconstitution, and anti-fibrosis therapy, have been supported by clinical and preclinical results.
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