[Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation]

Zhonghua Xue Ye Xue Za Zhi. 2023 Aug 14;44(8):660-666. doi: 10.3760/cma.j.issn.0253-2727.2023.08.008.
[Article in Chinese]

Abstract

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.

目的: 比较两种兔抗人胸腺细胞免疫球蛋白(rATG)预处理给药方案同胞全相合造血干细胞移植(MSD-HSCT)治疗恶性血液病的疗效。 方法: 纳入2020年10月至2022年4月在解放军总医院第一医学中心血液科接受含rATG 5 mg/kg预处理MSD-HSCT的32例患者,按照rATG给药方案分为4天给药组(4d-rATG组,16例)和2天给药组(2d-rATG组,16例),4d-rATG组移植前5~2 d给药,2d-rATG组移植前5、4 d给药。对两组患者临床资料进行回顾性分析,比较两组移植结局、移植前4 d至移植后28 d患者血清活性抗胸腺细胞球蛋白(ATG)浓度及移植后30、60、90 d淋巴细胞亚群重建情况。 结果: ①4d-rATG组、2d-rATG组移植后100 d急性移植物抗宿主病(GVHD)的累积发生率分别为25.0%(95%CI 7.8%~47.2%)、18.8%(95%CI 4.6%~40.2%)(P=0.605),1年慢性GVHD累积发生率分别为25.9%(95%CI 8.0%~48.6%)、21.8%(95%CI 5.2%~45.7%)(P=0.896),移植后1年累积复发率分别为37.5%(95%CI 18.9%~65.1%)、14.6%(95%CI 3.6%~46.0%)(P=0.135),1年总生存率分别为75.0%(95%CI 46.3%~89.8%)、100%(P=0.062)。②4d-rATG组、2d-rATG组患者总血清活性ATG浓度-时间曲线下面积(AUC)分别为36.11、35.89 UE/ml·d(P=0.984),4d-rATG组移植后AUC高于2d-rATG组(20.76 UE/ml·d对15.95 UE/ml·d,P=0.047)。③4d-rATG组、2d-rATG组移植后3个月CD8(+)T淋巴细胞计数分别为852(680~1968)个/μl、623(611~764)个/μl(P=0.037)。 结论: 4d-rATG方案与2d-rATG方案具有相近的GVHD预防作用;2d-rATG组CD8(+)T淋巴细胞重建优于4d-rATG组,可能与其移植后活性ATG浓度较低有关。.

Keywords: Allogeneic hematopoietic stem cell transplantation; Antithymocyte globulin; Pharmacokinetics; Relapsed.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Antilymphocyte Serum / therapeutic use
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Rabbits
  • Retrospective Studies
  • Siblings
  • Tissue Donors
  • Transplantation Conditioning

Substances

  • Antilymphocyte Serum