Mini-dose methotrexate combined with methylprednisolone as a first-line treatment for acute graft-versus-host disease: A phase 2 trial.

IF 4.7 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Zhengli Xu, Xiaodong Mo, Yuan Kong, Qi Wen, Tingting Han, Meng Lyu, Lanping Xu, Yingjun Chang, Xiaohui Zhang, Xiaojun Huang, Yu Wang
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Abstract

Background and objectives: Acute graft-versus-host disease (aGvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methylprednisolone (MP; 1-2 mg/kg/day) remains the standard first-line therapy for aGvHD, although no response is detected in nearly one-half of the patients with aGvHD. This study aimed to investigate the feasibility of mini-dose methotrexate (MTX) combined with standard-dose MP as a front-line therapy for aGvHD.

Materials and methods: A prospective Phase 2 clinical trial was performed to evaluate the safety and efficacy of 5 mg/m2 MTX combined with 1 mg/kg/day MP as the initial therapy in 31 patients with aGvHD. Moreover, the effects of MTX combined with MP were explored in a humanized xenogeneic murine model of aGvHD.

Results: The overall response and complete response rate at 7 days after the initial treatment were 100% and 83%, respectively. The overall response rate on day 28 was 87%. The complete response rates for aGvHD grades I, II, and III were 100% (6/6), 82% (18/22), and 66% (2/3), respectively. Grade 3 toxicities occurred in only three patients presenting with cytopenia. Importantly, MTX and MP demonstrated synergistic effects on ameliorating aGvHD in humanized xenogeneic murine model.

Conclusion: The current study suggests that mini-dose MTX combined with standard-dose MP could potentially become a novel first-line therapy for patients with aGvHD.

Abstract Image

Abstract Image

小剂量甲氨蝶呤联合甲基强的松龙作为急性移植物抗宿主病的一线治疗:一项2期试验
背景和目的:急性移植物抗宿主病(aGvHD)仍然是同种异体造血干细胞移植(alloo - hsct)后的主要并发症。甲基强的松龙(MP;1-2 mg/kg/天)仍然是aGvHD的标准一线治疗,尽管在近一半的aGvHD患者中没有发现反应。本研究旨在探讨小剂量甲氨蝶呤(MTX)联合标准剂量MP作为aGvHD一线治疗的可行性。材料与方法:对31例aGvHD患者进行前瞻性2期临床试验,评估5 mg/m2 MTX联合1 mg/kg/day MP作为初始治疗的安全性和有效性。此外,我们还在人源化异种aGvHD小鼠模型中探讨了MTX联合MP的作用。结果:初始治疗后7 d总有效率为100%,完全有效率为83%。第28天的总有效率为87%。aGvHD I、II和III级的完全缓解率分别为100%(6/6)、82%(18/22)和66%(2/3)。3级毒性仅发生在3例表现为细胞减少的患者中。重要的是,MTX和MP在人源化异种小鼠aGvHD模型中表现出协同效应。结论:目前的研究表明,小剂量MTX联合标准剂量MP可能成为aGvHD患者的一种新的一线治疗方法。
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来源期刊
Journal of Translational Internal Medicine
Journal of Translational Internal Medicine MEDICINE, GENERAL & INTERNAL-
CiteScore
5.50
自引率
8.20%
发文量
41
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