Treatment of refractory graft-versus-host disease

Hematopoietic stem cell transplantation (HSCT), as one of the most effective and promising treatments for malignant hematological diseases, severe immunodeficiency diseases and bone marrow hematopoietic failure, has been increasingly used in clinical practice, especially allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which has saved many patients’ lives. -HSCT has saved the lives of many patients. However, graft versus host disease (GVHD) is still the leading cause of death associated with bone marrow transplantation or hematopoietic stem cell transplantation. Successful implantation of HSCT is a prerequisite for the therapeutic effect of HSCT. In HSCT patients, most of whom have undergone multiple chemotherapies, the microenvironment of the bone marrow is damaged and therefore its hematopoietic support is reduced. Pre-transplantation pretreatment with high doses of chemotherapy/radiotherapy leading to more severe marrow stromal damage, HLA mismatched transplantation, insufficient number of transfused HSCs due to donor differences and the occurrence of GVHD can lead to failed or delayed HSC implantation, thus increasing transplantation-related mortality. The integrity of the bone marrow hematopoietic microenvironment is crucial for hematopoietic reconstitution after HSCT. Recently, there have been some clinical reports on the treatment of severe graft-versus-host disease with MSCs combined with HSCT co-transplantation and MSC infusion. In vitro culture studies have demonstrated that bone marrow MSC have a strong expansion capacity and can be expanded in vitro in large numbers with the ability to self-renew; MSC have strong hematopoietic support and immunomodulatory effects. An earlier phase I clinical study conducted by Lazarus et al. in 1995 showed that bone marrow-derived MSC can be safely imported after 4-7 weeks of in vitro expansion into In 2005, Laxarus reported that the incidence of acute GVHD was 28% and the incidence of chronic GVHD was 61% in 46 patients who received combined transplantation of HLA-identical donor-derived HSC and ex vivo expanded MSC, and the 2-year disease-free survival was 53%, and the incidence of acute and chronic GVHD was lower than that of allogeneic stem cells in the same period. In 2004, LeBlanc et al. reported an earlier case of acute visceral graft-versus-host disease of degree IV after infusion of third-party-derived hemizygous donor MSCs for the treatment of hormone therapy-naïve allogeneic transplantation from an unrelated donor, with significant recent results. The current preliminary clinical results show that co-transplantation of HSC and MSCs is safe and feasible, promotes the implantation of hematopoietic stem cells and reduces the incidence of post-transplantation graft-versus-host disease, improves transplantation outcomes, and reduces recent mortality. In addition, MSCs are widely distributed, easy to obtain, and lack immunogenicity, which makes it possible to widely use MSCs in clinical HSC transplantation.