ECM, KFC, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Sci Rep. 2018 May 29;8(1):8293. doi: 10.1038/s41598-018-26033-z.
Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure).
NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.
白消安（Bu）是一种骨髓清除药物，用于造血干细胞移植前的调理。Bu 主要通过谷胱甘肽结合代谢，该反应消耗肝脏中的谷胱甘肽。N-乙酰-L-半胱氨酸（NAC）是一种用于治疗对乙酰氨基酚肝毒性的谷胱甘肽前体。NAC 不干扰 Bu 的骨髓清除作用。我们研究了 Bu 调理期间同时给予 NAC 治疗对肝酶以及临床结果的影响。在 Bu 调理开始时，54 例患者给予预防性 NAC 治疗。将这些患者与未接受 NAC 治疗的 54 例历史匹配的对照组进行比较。在接受 NAC 治疗的患者中，与起始值相比，天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）在调理后明显（P < 0.05）降低。在 NAC 组中，那些起始值显著升高的患者的肝酶恢复正常。对照组未观察到酶水平的显著下降。此外，NAC 既不影响 Bu 动力学，也不影响临床结果（窦状隙阻塞综合征发生率、移植物抗宿主病和/或移植物失败）。
NAC 是 Bu 调理期间肝毒性的潜在预防治疗方法。NAC 治疗并未改变 Bu 的动力学或影响临床结果。
