关键词: 脐带间充质干细胞, 单倍体相合造血干细胞移植, 急性移植物抗宿主病, 恶性血液病, 安全性

Abstract: BACKGROUND: HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies. In recent years, the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing. At present, the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China, but this model requires the collection of donor bone marrow fluid, which increases the pain and risk of the donor.
OBJECTIVE: To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases.
METHODS: Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3. Among them, 19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation, and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells. The study was approved by the Ethics Committee of Henan Provincial People’s Hospital. The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells (1×106/kg) on the day of transplantation, followed by peripheral blood hematopoietic stem cells 6 hours later. In the bone marrow group, donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation. After transplantation, rabbit anti-human thymocyte immunoglobulin, cyclosporine A, mycophenolate mofetil, and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients.
RESULTS AND CONCLUSION: No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells. There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate [100% (19/19) vs. 96.8%(30/31), P > 0.05], median duration for neutrophil engraftment (14 days vs.15 days, P > 0.05) and median duration for platelet engraftment (20 days vs.19 days, P > 0.05). The incidence of grade II-IV acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group [21.1% (4/19) vs. 58.1% (18/31), P = 0.01]. There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease [21.1% (4/19) vs. 25.8% (8/31), P > 0.05], the relapse rates [15.8% (3/19) vs. 16.1% (5/31), P > 0.05] and the incidence of early cytomegalovirus viremia [42.1% (8/19) vs. 35.5% (11/31), P > 0.05], and the 2-year overall survival rate [68.4% (10/19) vs. 70.9% (16/31), P > 0.05]. It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases, which reduced the incidence of acute graft-versus-host disease after transplantation, did not increase the incidence of chronic graft-versus-host disease, recurrence rate and early cytomegalovirus viremia, and reduced the pain and risk of donor pulp extraction.

Key words: umbilical cord mesenchymal stem cell, haploidentical hematopoietic stem cell transplantation, acute graft-versus-host disease, malignant hematological disease, safety