Hings I M, Filipovich A H, Miller W J, Blazar B L, McGlave P B, Ramsay N K, Kersey J H, Weisdorf D J
Department of Medicine, University of Minnesota, Minneapolis 55455.
Transplantation. 1993 Sep;56(3):577-80. doi: 10.1097/00007890-199309000-00016.
We report the results of a controlled study in which BMT patients with moderate/severe acute graft-versus-host disease (GVHD) who responded to primary treatment with corticosteroids were prospectively randomized to short versus long taper of their steroid doses. Thirty patients with moderate/severe acute GVHD who responded by 14 days were eligible for random assignment of their steroid tapering schedule. Patients in the short taper group received a total PRED dose of 2275 mg/m2 over 86 days, whereas those in the long taper group received 6300 mg/m2 over 147 days. Patients in the long taper group achieved resolution of acute GVHD after a median of 30 days of therapy (range 6-30), whereas those receiving the short taper resolved after a median of 42 days (12-74) (P = 0.01). After 8 weeks of therapy, only 2 of 13 evaluable long taper and 3 of 13 short taper patients still had active GVHD. The median PRED dose required to achieve complete resolution of acute GVHD was not different between the two groups: 1300 mg/m2 for the long taper patients and 1800 mg/m2 for the short taper patients. Importantly, the incidence of chronic GVHD and survival at 6 months was similar in the 2 groups. The incidence of steroid-related complications was similar, as well. This study suggests that the rapid administration of high-dose PRED to a cumulative dose of 2000 mg/m2 might lead to complete and prompt resolution of acute GVHD in the majority of patients and that rapid PRED taper might provide a mechanism for minimizing steroid-related morbidity. Further investigation and formal studies of the dose-response relationships and kinetics of steroid administration may lead to improvement in the management of acute GVHD.
我们报告了一项对照研究的结果，该研究中，对皮质类固醇初始治疗有反应的中度/重度急性移植物抗宿主病（GVHD）的骨髓移植（BMT）患者被前瞻性随机分为类固醇剂量短程减量组和长程减量组。14天内有反应的30例中度/重度急性GVHD患者符合随机分配类固醇减量方案的条件。短程减量组患者在86天内接受的泼尼松（PRED）总剂量为2275mg/m²，而长程减量组患者在147天内接受的剂量为6300mg/m²。长程减量组患者在治疗中位数30天（范围6 - 30天）后急性GVHD得到缓解，而接受短程减量的患者在中位数42天（12 - 74天）后缓解（P = 0.01）。治疗8周后，13例可评估的长程减量患者中只有2例、13例短程减量患者中有3例仍有活动性GVHD。两组实现急性GVHD完全缓解所需的PRED中位数剂量无差异：长程减量组患者为1300mg/m²，短程减量组患者为1800mg/m²。重要的是，两组慢性GVHD的发生率和6个月时的生存率相似。类固醇相关并发症的发生率也相似。这项研究表明，快速给予高剂量PRED至累积剂量2000mg/m²可能会使大多数患者的急性GVHD完全且迅速缓解，快速的PRED减量可能为将类固醇相关发病率降至最低提供一种机制。对类固醇给药的剂量反应关系和动力学进行进一步研究和正式研究可能会改善急性GVHD的管理。
