Agrawal Vaibhav, Ranganath Praveen, Ervin Kirsten D, Schmidt Caitlin A, Cox Elizabeth A, Nelson Robert P, Schwartz Jennifer E, Zaid Mohammad Abu, Abonour Rafat, Robertson Michael J, Brinda Bryan J, Griffin Shawn P, Thakrar Teresa C, Farag Sherif S
Department of Medicine, Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
Bone Marrow and Blood Stem Cell Transplantation Program, Indiana University Health, Indianapolis, IN, USA.
Bone Marrow Transplant. 2021 Jan;56(1):121-128. doi: 10.1038/s41409-020-0987-1. Epub 2020 Jul 4.
Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT). Sirolimus plus tacrolimus is an accepted regimen for graft-versus-host disease (GVHD) prophylaxis, with both agents implicated as risk factors for SOS. We analyzed 260 consecutive patients who underwent allogeneic HSCT following myeloablative conditioning using total body irradiation (TBI)-based (n = 151) or chemotherapy only (n = 109) regimens, with sirolimus plus tacrolimus for GVHD prophylaxis. SOS occurred in 28 patients at a median of 22 (range, 12-58) days. Mean sirolimus trough levels were higher between days 11 and 20 following transplant in patients who developed SOS (10.3 vs. 8.5 ng/ml, P = 0.008), with no significant difference in mean trough levels between days 0 and 10 (P = 0.67) and days 21-30 (P = 0.37). No differences in mean tacrolimus trough levels during the same time intervals were observed between those developing SOS and others. On multivariable analysis, a mean sirolimus trough level ≥ 9 ng/ml between days 11 and 20 increased the risk of SOS (hazard ratio 3.68, 95% CI: 1.57-8.67, P = 0.003), together with a longer time from diagnosis to transplant (P = 0.004) and use of TBI (P = 0.006). Our results suggest that mean trough sirolimus levels ≥ 9 ng/mL between days 11 and 20 post transplant may increase the risk of SOS and should be avoided.
窦性阻塞综合征（SOS）是造血干细胞移植（HSCT）的一种严重并发症。西罗莫司联合他克莫司是预防移植物抗宿主病（GVHD）的一种公认方案，这两种药物均被认为是SOS的危险因素。我们分析了260例连续接受异基因HSCT的患者，这些患者采用基于全身照射（TBI）的清髓预处理方案（n = 151）或仅化疗方案（n = 109），并使用西罗莫司联合他克莫司预防GVHD。28例患者发生SOS，中位时间为22天（范围12 - 58天）。发生SOS的患者在移植后第11至20天的西罗莫司平均谷浓度较高（10.3对8.5 ng/ml，P = 0.008），在第0至10天（P = 0.67）和第21至30天（P = 0.37）平均谷浓度无显著差异。在发生SOS的患者与其他患者之间，在相同时间间隔内他克莫司平均谷浓度未观察到差异。多变量分析显示，移植后第11至20天西罗莫司平均谷浓度≥9 ng/ml会增加SOS风险（风险比3.68，95%置信区间：1.57 - 8.67，P = 0.003），同时从诊断到移植的时间较长（P = 0.004）以及使用TBI（P = 0.006）。我们的结果表明，移植后第11至20天西罗莫司平均谷浓度≥9 ng/mL可能会增加SOS风险，应避免这种情况。
