Sequential Administration of WJ-MSCs for the Treatment of GvHD Refractory to Second Line Treatment

Overview

Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant hemopathies, but highlights the limitations of long-term results due to the high toxicity of the procedure and the development of Graft versus Host Disease (GVHD). Conventional treatments for GVHD have limited success rates, and some patients may be refractory to ruxolitinib, a second-line treatment option. As a result, there is a need to explore alternative immuno-modulatory therapies, such as the use of Wharton's jelly mesenchymal stem cells (WJ-MSCs). The research question aims to investigate the safety and potential benefits of sequentially infusing thawed or expanding allogeneic WJ-MSCs in the treatment of acute GVHD refractory to second-line treatment in patients from the Colombian population. This pilot clinical study is being conducted to address the unmet need for patients who develop GVHD resistant to ruxolitinib.

In recent decades, the number of HSCTs has significantly increased, as it is considered the ideal therapeutic approach for a wide range of hematological diseases. However, GVHD is the most common and severe complication following transplantation, and it remains the major limiting factor for the success of HSCT. It has been reported that the incidence of acute GVHD is approximately 50% in patients who receive HSCT from an HLA-matched donor, and it increases in cases of HLA-mismatched donors, despite having prophylactic treatment. Patients who develop GVHD have a poor prognosis, with a survival rate ranging from 5-25% depending on the severity of the disease. This is strongly related to the lack of effective treatments. In addition to the high morbidity and mortality, GVHD represents a significant financial burden for public healthcare systems worldwide. A recent study in 2018 in the United States reported that the cost of complete remission for a 6-month period with ruxolitinib, one of the most commonly used treatments for both acute and chronic GVHD, was $1,187,657 USD. In this context, the American Society for Blood and Marrow Transplantation considers MSCs as a prominent therapeutic tool for the treatment of GVHD, as they significantly improve both the symptoms of the most frequently affected organs (skin, liver, and intestines) and the treatment response parameters and overall survival. Colombia is not exempt from this issue; the rise of HSCT in our country is evident. Therefore, the development of a novel and effective therapeutic strategy for GVHD is a priority and demands further scientific research. Finally, with the development of this pilot study, the aim is to lay the groundwork for conducting medium- and large-scale clinical trials in our Colombian population, where clinical studies with this type of therapeutic approach have not yet been conducted.