两种兔抗人胸腺细胞免疫球蛋白给药方案同胞全相合造血干细胞移植治疗恶性血液病的临床研究

OBJECTIVE: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin（rATG）of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation（MSD-HSCT）. METHODS: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group（16 cases）, who received antithymocyte globulin（ATG）from day −5 to day −2, and the 2d-rATG group（16 cases）, who received ATG from day −5 to day −4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin（ATG）in patients from −4 days to 28 days after graft infusion（+28 days）, and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. RESULTS: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0％（95％CI 7.8％–47.2％）and 18.8％（95％CI 4.6％–40.2％）（P＝0.605）in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9％（95％CI 8.0％–48.6％）and 21.8％（95％CI 5.2％–45.7％）（P＝0.896）. The 1-year cumulative incidence of relapse was 37.5％（95％CI 18.9％–65.1％）and 14.6％（95％CI 3.6％–46.0％）（P＝0.135）, and the 1-year probabilities of overall survival were 75.0％（95％CI 46.3％–89.8％）and 100％（P＝0.062）. The total area under the curve（AUC）of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively（P＝0.984）. The AUC was higher in the 4d-rATG group than that in the 2d-rATG group（20.76 UE/ml·d vs 15.95 UE/ml·d, P＝0.047）. Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group（623 cells/µl vs 852 cells/µl, P＝0.037）. CONCLUSION: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.