Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain.
Bone Marrow Transplant. 2022 Jul;57(7):1095-1100. doi: 10.1038/s41409-022-01689-4. Epub 2022 Apr 27.
Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication after allogeneic stem cell transplantation (allo-HCT). However, there is no uniform consensus on the optimal strategy for SOS prevention. Ursodeoxycholic acid is the most used regimen, even though its administration is challenging in recipients unable to tolerate oral medication. Defibrotide was recently studied in a phase 3 trial, but enrollment was stopped early due to futility. Low-dose unfractionated heparin (UFH) is an alternative strategy. However, its efficacy is reputed but unproven increased risk of bleeding has not been fully established. We evaluated 514 adult allo-HCT recipients who received SOS prophylaxis with low-dose UFH. Bleeding complications occurred in 12 patients 2.3% of patients of which only 2 (0.4%) had significant grade 3 bleeding. Only 14 patients were diagnosed with hepatic SOS. Univariate analysis showed that day 100 SOS was higher in recipients of unmodified grafts when compared to CD34+ selected ex vivo T-cell depleted grafts (p ≤ 0.001), and patients with hepatitis B and/or C exposure pre-HCT (p = 0.028). Overall, UFH was well tolerated and associated with a low incidence of subsequent hepatic SOS. Low-dose UFH prophylaxis can be considered in select patients who cannot tolerate oral ursodiol.
肝窦阻塞综合征(SOS)是异基因干细胞移植(allo-HCT)后的一种严重并发症。然而,对于 SOS 的预防,目前还没有统一的共识。熊去氧胆酸是最常用的方案,尽管对于不能耐受口服药物的患者来说,其给药具有挑战性。地塞米松在一项 3 期试验中进行了研究,但由于无效而提前停止入组。低剂量未分级肝素(UFH)是一种替代策略。然而,其疗效虽已得到认可,但出血风险增加尚未得到充分证实。我们评估了 514 名接受低剂量 UFH 预防 SOS 的成年 allo-HCT 受者。12 名患者(2.3%)发生出血并发症,其中只有 2 名(0.4%)有明显的 3 级出血。仅 14 名患者被诊断为肝 SOS。单因素分析显示,与 CD34+体外 T 细胞去除的修饰移植物相比,未修饰移植物的 100 天 SOS 更高(p≤0.001),且在 allo-HCT 前有乙型肝炎和/或丙型肝炎暴露的患者(p=0.028)。总体而言,UFH 耐受性良好,与随后发生的肝 SOS 发生率较低相关。对于不能耐受口服熊去氧胆酸的患者,可考虑低剂量 UFH 预防。