Novel and Promising Strategies for Therapy of Post-Transplant Chronic GVHD

Abstract

Despite the achievements that have increased viability after the transplantation of allogeneic hematopoietic stem cells (aHSCT), chronic graft-versus-host disease (cGVHD) remains the main cause of late complications and post-transplant deaths. At the moment, therapy alternatives demonstrate limited effectiveness in steroid-refractory illness; in addition, we have no reliable data on the mechanism of this condition. The lack of drugs of choice for the treatment of GVHD underscores the significance of the design of new therapies. Improved understanding of the mechanism of chronic GVHD has secured new therapy goals, and organized diagnostic recommendations and the development of medical tests have ensured a general language and routes for studies in this field. These factors, combined with the rapid development of pharmacology, have helped speed up the search of medicines and medical studies regarding chronic GVHD. At present, we can hope for success in curing this formidable complication. This review summarizes the latest clinical developments in new treatments for chronic GVHD.

Mesenchymal Stem Cell Applications in Graft Versus Host Disease

“…These cytokines activate donor alloreactive T cells along with antigen-presenting cells, causing host tissue damage through the expansion of donor helper T cells (including Th17), cytotoxic T lymphocytes, and natural killer cells. Inflammatory immune responses against these cells lead to significant tissue harm, affecting various organs and body areas such as the skin, oral cavity, eyes, digestive system, liver, lungs, joints, and reproductive tract and promoting GvHD (14)(15)(16)(17).…”

“…Treatment options for GvHD include the use of broad-spectrum immunosuppressives, but these treatments may be ineffective and could potentially increase the risk of cancer recurrence (14,15,17). The standard treatment depends on the affected organ or site and can be either local or systemic, with more adverse effects associated with systemic treatments.…”

Identification of Fibroinflammatory and Fibrotic Transcriptomic Subsets of Human Cutaneous Sclerotic Chronic Graft-Versus-Host Disease

“…Most patients with cGVHD are initially treated with immunosuppressive therapy (corticosteroids, calcineurin inhibitors, mTOR inhibitors). Recently, 3 targeted options were Food and Drug Administration approved for refractory disease, which inhibit JAKs, ROCK2, and Bruton’s tyrosine kinase ( Kostareva et al, 2022 ). Nonetheless, management is complicated by heterogeneous clinical presentations and variable responsiveness to both conventional immunosuppressive and targeted therapies.…”

Identification of single nucleotide polymorphisms (SNPs) associated with chronic graft-versus-host disease in patients undergoing allogeneic hematopoietic cell transplantation

“…Clinical treatment of cGVHD aims to improve and to stabilize organ involvement and symptoms, but also to improve quality of life and survival [ 10 ]. Guidelines recommend no treatment or local application of steroids or other immunosuppressive drugs if mild cGVHD [ 11 ].…”