IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy.
IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
Cancer Med. 2022 Feb;11(3):618-629. doi: 10.1002/cam4.4390. Epub 2021 Dec 30.
In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno-occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver-related complications during clinical trials and real-life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow-up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate-severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver-related changes, especially with the severity of portal hypertension (PH)-related complications. Pre-transplant LSM was higher in patients receiving IO when compared with a control cohort. PH-related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.
在成人患者中，急性淋巴细胞白血病（ALL）是一种罕见的血液系统恶性肿瘤，其治愈率低于 50%，且常复发。传统疗法下，复发或难治性（R/R）ALL 患者的生存时间可能以月来计算；在这些患者中，奥滨尤妥珠单抗（IO）是一种有效的治疗方法。临床试验和实际应用中发现 IO 会增加静脉阻塞性疾病/肝窦阻塞综合征（VOD/SOS）、肝损伤和各种程度肝相关并发症的风险；然而，该人群尚未建立肝监测方案。在我们的机构中，21 例 R/R ALL 患者接受 IO（中位 6 个 IO 剂量）治疗，前瞻性地进行了肝监测，包括临床评估、超声和肝硬度测量（LSM）的生化检查。中位随访 17.2 个月后，报告了 2 例 SOS 事件（均发生在异基因移植后），为 IO 潜在相关的临床相关不良事件。几乎所有患者均出现轻度改变，四分之一患者出现中重度肝生化改变。在生化值中，AST 和 ALP 显示与 IO 给药相关的增加。每接受一个 IO 疗程，LSM 呈线性增加。基线 LSM 与肝相关变化相关，尤其是与门静脉高压（PH）相关并发症的严重程度相关。与对照组相比，接受 IO 治疗的患者移植前 LSM 更高。近 77%的患者出现 PH 相关并发症，分别有 38%和 14%出现临床显著 PH 和腹水发展。这一前瞻性经验为设计接受 IO 治疗的患者的肝监测计划提供了依据。LSM 在该方案中可能具有重要意义，它是一种快速有效的筛查方法，可定量地与肝变化相关联。
