BMTCI H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
GI/Hepatology, Fred Hutchinson Cancer Research Center, Seattle, USA.
Bone Marrow Transplant. 2019 Jan;54(1):85-89. doi: 10.1038/s41409-018-0233-2. Epub 2018 Jun 12.
Sirolimus-based graft vs. host disease (GVHD) prophylaxis is associated with higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation (HCT). However, whether the clinical manifestations and prognosis of VOD/SOS differs when diagnosed in the setting of sirolimus-based GVHD prophylaxis is not well studied. To address this question, we examined presenting features and treatment outcome of VOD/SOS cases identified in a large retrospective cohort of consecutive HCT procedures (n = 818 total, sirolimus (SIR)/tacrolimus (TAC) n = 308, and methotrexate (MTX) or mycophenolate mofetil (MMF)/TAC n = 510). In multivariate analysis, sirolimus-based GVHD prophylaxis (p = 0.006, HR 3.33, 1.94-5.7) increased risk for VOD/SOS. A total of 58 patients were clinically diagnosed with VOD/SOS (SIR/TAC 38/308, 12.3%, vs. MTX or MMF/TAC 20/510, 3.9%). VOD/SOS diagnosed following SIR/TAC prophylaxis demonstrated later time of onset (median 39 vs. 26 days; p = 0.005), less severe hyperbilirubinemia (Bili > 2, 65% vs. 90% p = 0.04), lesser degree of weight gain (weight gain > 5%, 52% vs 80%, p = 0.04), and more frequent complete resolution of hepatic injury (79% vs. 55%, p = 0.05). Presenting features and natural history of VOD/SOS in the context of SIR/TAC GVHD prophylaxis differ and thus warrant particular clinical attention to later hepatic injury in these patients.
西罗莫司为基础的移植物抗宿主病（GVHD）预防与异基因造血细胞移植（HCT）后静脉闭塞病/窦状隙阻塞综合征（VOD/SOS）的发生率较高相关。然而，在西罗莫司为基础的 GVHD 预防的情况下诊断 VOD/SOS 的临床表现和预后是否不同，目前研究还不够充分。为了解决这个问题，我们检查了在一项大型回顾性连续 HCT 程序队列研究（共 818 例，西罗莫司（SIR）/他克莫司（TAC）n=308 例，甲氨蝶呤（MTX）或吗替麦考酚酯（MMF）/TAC n=510 例）中确定的 VOD/SOS 病例的临床表现和治疗结果。多变量分析显示，西罗莫司为基础的 GVHD 预防（p=0.006，HR 3.33，1.94-5.7）增加了 VOD/SOS 的风险。共有 58 例患者被临床诊断为 VOD/SOS（SIR/TAC 38/308，12.3%，MTX 或 MMF/TAC 20/510，3.9%）。SIR/TAC 预防后诊断的 VOD/SOS 发病时间较晚（中位数 39 天 vs. 26 天；p=0.005），胆红素升高（Bili>2，65% vs. 90%，p=0.04）、体重增加（体重增加>5%，52% vs. 80%，p=0.04）和肝脏损伤完全缓解（79% vs. 55%，p=0.05）的频率较低。在 SIR/TAC GVHD 预防的情况下，VOD/SOS 的临床表现和自然病史不同，因此需要特别注意这些患者的后期肝脏损伤。
