Chiu Yu-Hsiang, Drijver Anouk, Admiraal Rick, van Rhenen Anna, Nierkens Stefan, van Laar Jacob M, Spierings Julia
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Division of Rheumatology/Immunology/Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei.
J Scleroderma Relat Disord. 2023 Oct;8(3):241-246. doi: 10.1177/23971983231188232. Epub 2023 Jul 24.
Autologous haematopoietic stem cell transplantation improves event-free survival and lung function and reduces skin thickening in patients with progressive diffuse cutaneous systemic sclerosis. Anti-thymocyte globulin is a key lymphoablative constituent of conditioning protocols and is administered in a weight-based dosage. However, whether anti-thymocyte globulin exposure contributes to response to autologous haematopoietic stem cell transplantation and lymphocyte reconstitution in diffuse cutaneous systemic sclerosis patients is unknown. We aimed to explore the relationship between anti-thymocyte globulin exposure, lymphocyte reconstitution and treatment response in diffuse cutaneous systemic sclerosis patients undergoing autologous haematopoietic stem cell transplantation.
A retrospective cohort of 15 diffuse cutaneous systemic sclerosis patients undergoing autologous haematopoietic stem cell transplantation was performed. Clinical characteristics and routine laboratory results were retrieved from electronic medical records. Anti-thymocyte globulin concentrations were measured in cryopreserved plasma samples at four time points (day 1 and week 1, 2 and 4) after stem cell reinfusion. Anti-thymocyte globulin exposure was estimated using a validated population pharmacokinetic model.
During a median follow-up of 45 months (interquartile range 19-66), 11 (73%) patients had a treatment response, and 4 (27%) were non-responders. Although all patients received the same weight-based anti-thymocyte globulin dosage, 7.5 mg/kg divided over 3 days, anti-thymocyte globulin exposure varied. Anti-thymocyte globulin exposure was higher in responders than in non-responders (163 AUday/mL (interquartile range 153-183) and 137 AUday/mL (interquartile range 101-149), respectively, = .026). Anti-thymocyte globulin exposure was not correlated with lymphocyte reconstitution or infection rate.
Weight-based dosing of anti-thymocyte globulin results in variable anti-thymocyte globulin exposure and treatment response across individuals.
自体造血干细胞移植可改善无事件生存期和肺功能，并减轻进行性弥漫性皮肤系统性硬化症患者的皮肤增厚。抗胸腺细胞球蛋白是预处理方案中的关键淋巴细胞清除成分，按体重给药。然而，抗胸腺细胞球蛋白暴露是否有助于弥漫性皮肤系统性硬化症患者对自体造血干细胞移植的反应及淋巴细胞重建尚不清楚。我们旨在探讨接受自体造血干细胞移植的弥漫性皮肤系统性硬化症患者中抗胸腺细胞球蛋白暴露、淋巴细胞重建与治疗反应之间的关系。
对15例接受自体造血干细胞移植的弥漫性皮肤系统性硬化症患者进行回顾性队列研究。从电子病历中获取临床特征和常规实验室结果。在干细胞回输后的四个时间点（第1天、第1周、第2周和第4周），对冷冻保存的血浆样本中的抗胸腺细胞球蛋白浓度进行测量。使用经过验证的群体药代动力学模型估算抗胸腺细胞球蛋白暴露量。
在中位随访45个月（四分位间距19 - 66个月）期间，11例（73%）患者有治疗反应，4例（27%）无反应。尽管所有患者接受相同的基于体重的抗胸腺细胞球蛋白剂量，即7.5 mg/kg分3天给药，但抗胸腺细胞球蛋白暴露量各不相同。有反应者的抗胸腺细胞球蛋白暴露量高于无反应者（分别为1,63 AU天/毫升（四分位间距153 - 183）和137 AU天/毫升（四分位间距101 - 149），P = 0.026）。抗胸腺细胞球蛋白暴露量与淋巴细胞重建或感染率无关。
基于体重的抗胸腺细胞球蛋白给药导致个体间抗胸腺细胞球蛋白暴露量和治疗反应各不相同。
