N-Acetylcysteine as Therapy for Transplantation- Associated Thrombotic Microangiopathy

Summary

This multicenter, prospective, single-arm clinical trial aims to evaluate the efficacy and safety of N-acetylcysteine (NAC) for treating Transplantation-Associated Thrombotic Microangiopathy (TA-TMA), a severe complication of hematopoietic stem cell transplantation characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury, with an incidence of 4%-30%. Current treatments, including plasma exchange (response rate \<10%) and costly complement inhibitors like Eculizumab (71% response) which are not widely accessible, are inadequate. Inspired by NAC's success in treating the related condition thrombotic thrombocytopenic purpura (TTP) and supported by bioinformatic analyses of patient data revealing enhanced oxidative stress pathways and identifying NAC as a potential targeted therapy, our prior study demonstrated that NAC prophylaxis significantly reduces TA-TMA incidence and improves survival. Building on this promising foundation, this study will enroll patients meeting TA-TMA diagnostic criteria for NAC treatment, assessing its potential as a safe, effective, and affordable therapeutic option.

Timeline

Start

2024-05-01

Primary completion

2026-12-31

Completion

2026-12-31

Publications

• Results Pan T, Qi J, Tang Y, Yao Y, Chen J, Wang H, Yang J, Xu X, Shi Q, Liu Y, He X, Chen F, Ma X, Hu X, Wu X, Wu D, Han Y. N-Acetylcysteine as Prophylactic Therapy for Transplantation-Associated Thrombotic Microangiopathy: A Randomized, Placebo-Controlled Trial. Transplant Cell Ther. 2022 Nov;28(11):764.e1-764.e7. doi: 10.1016/j.jtct.2022.07.029. Epub 2022 Aug 5.
• Results Qi J, Hu S, He X, Pan T, Yang L, Zhang R, Tang Y, Wu D, Han Y. N-Acetyl-L-Cysteine Potentially Inhibits Complement Activation in Transplantation-Associated Thrombotic Microangiopathy. Transplant Cell Ther. 2022 Apr;28(4):216.e1-216.e5. doi: 10.1016/j.jtct.2021.12.018. Epub 2021 Dec 31.
• Results Tersteeg C, Roodt J, Van Rensburg WJ, Dekimpe C, Vandeputte N, Pareyn I, Vandenbulcke A, Plaimauer B, Lamprecht S, Deckmyn H, Lopez JA, De Meyer SF, Vanhoorelbeke K. N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood. 2017 Feb 23;129(8):1030-1038. doi: 10.1182/blood-2016-09-738856. Epub 2016 Dec 23.
• Results Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, Ni H, Lopez JA. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest. 2011 Feb;121(2):593-603. doi: 10.1172/JCI41062. Epub 2011 Jan 25.
• Results Zhang R, Zhou M, Qi J, Miao W, Zhang Z, Wu D, Han Y. Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis. Front Immunol. 2021 Jan 20;11:564647. doi: 10.3389/fimmu.2020.564647. eCollection 2020.
• Results Schoettler ML, Carreras E, Cho B, Dandoy CE, Ho VT, Jodele S, Moissev I, Sanchez-Ortega I, Srivastava A, Atsuta Y, Carpenter P, Koreth J, Kroger N, Ljungman P, Page K, Popat U, Shaw BE, Sureda A, Soiffer R, Vasu S. Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research. Transplant Cell Ther. 2023 Mar;29(3):151-163. doi: 10.1016/j.jtct.2022.11.015. Epub 2022 Nov 25.

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