Umbilical Cord Mesenchymal Stem Cells in the Treatment of Moderate/Severe Chronic Graft-versus-host Disease

Graft Vs Host Disease Clinical Trial

Official title: Clinical Trial of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Moderate/Severe Chronic Graft-versus-host Disease

Status Recruiting

Clinical Trial Summary

cGVHD is a systemic disease with multi-system damage similar to autoimmune and other immune diseases. It can affect multiple organs such as skin, liver, kidney, and peripheral nerves, causing a serious decline in the quality of life of patients, and death in the late stage of transplantation. According to the cGVHD prognostic risk scoring system (revised Risk Group) revised by the European Society for Blood and Bone Marrow Transplantation (EBMT) in 2017, the 3-year survival rate of patients with rRG1 (0-3 points) is about 93.3 ± 6.4%, and rRG2 (4-6 points) about 84.9 ± 3.4%, rRG3 (7-9 points) about 70.9 ± 4.4%, rRG4 (≥10 points) about 32.0 ± 1.1%, it can be seen that moderate to severe cGVHD directly affects the survival of allo-HSCT patients.

Once moderate or severe cGVHD is diagnosed, glucocorticoids with or without calcineurin inhibitor (CNI) are first-line drugs, but the effective rate is less than 50%, and the prognosis of hormone-resistant severe cGVHD is extremely poor even if second-line treatment is added. Second-line treatments include monoclonal antibodies, immunosuppressants, chemotherapy drugs, phototherapy or others. Most of them cannot improve the long-term survival rate. The main reason is that these treatments suppress immunity for a long time, which increases the risk of infection and reduces the survival rate. In this context, the treatment of mesenchymal stromal stem cells (MSCs) provides a new path for clinical treatment of cGVHD.

Clinical Trial Description

Chronic graft-versus-host disease (cGVHD) refers to the clinicopathological synthesis of lymphocytes from the donor attacking the recipient's organs during the process of rebuilding the donor's immunity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) Signs (including classic cGVHD and overlap syndrome) are one of the main complications after transplantation, with an incidence of 30% to 70%. cGVHD is a systemic disease with multi-system damage similar to autoimmune and other immune diseases. It can affect multiple organs such as skin, liver, kidney, and peripheral nerves, causing a serious decline in the quality of life of patients, and death in the late stage of transplantation. main reason. According to the cGVHD prognostic risk scoring system (revised Risk Group) revised by the European Society for Blood and Bone Marrow Transplantation (EBMT) in 2017, the 3-year survival rate of patients with rRG1 (0-3 points) is about 93.3 ± 6.4%, and rRG2 (4-6 points) About 84.9 ± 3.4%, rRG3 (7-9 points) about 70.9 ± 4.4%, rRG4 (≥10 points) about 32.0 ± 1.1%, it can be seen that moderate to severe cGVHD directly affects the survival of allo-HSCT patients.

Once moderate or severe cGVHD is diagnosed, glucocorticoids with or without calcineurin inhibitor (CNI) are first-line drugs, but the effective rate is less than 50%, and the prognosis of hormone-resistant severe cGVHD is extremely poor even if second-line treatment is added. Second-line treatments include monoclonal antibodies, immunosuppressants, chemotherapy drugs, phototherapy or others. Most of them cannot improve the long-term survival rate. The main reason is that these treatments suppress immunity for a long time, which increases the risk of infection and reduces the survival rate. In this context, the treatment of mesenchymal stromal stem cells (MSCs) provides a new path for clinical treatment of cGVHD.

In 2002, Frassoni reported for the first time that MSCs expanded in vitro were used to evaluate the efficacy of allo-HSCT. Allo-HSCT transplanted patients with hematological malignancies were enrolled. MSCs were derived from the donor's bone marrow. After expanded in vitro, participants were combined with the donor's hematopoietic stem cells for reinfusion. As a result, the incidence of aGVHD in the MSCs expansion group and cGVHD within 6 months was significantly lower in the control group, the 6-month OS was significantly higher than that in the control group, and there was no significant difference in the recurrence rate. Subsequently, in 2004, Le Blanc and others successfully used third-party MSCs to successfully treat a refractory grade IV intestinal combined with liver aGVHD for the first time. Subsequently, MSCs were increasingly used in clinical studies for the treatment of GVHD. More clinical trials have shown that umbilical cord-derived MSCs cultured in vitro can not only promote the implantation of hematopoietic stem cells (HSC), but also reduce the incidence of severe GVHD in patients, showing a good therapeutic effect. ;

Related Conditions & MeSH terms

• Graft Vs Host Disease

• NCT number: NCT05152160
• Study type: Interventional
• Source: Shenzhen University General Hospital
• Contact: Li Yu
• Phone: +8675521839178
• Email: liyu@vip.163.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 1, 2021
• Completion date: August 2024