Real-world analysis of strategies to prevent thrombosis and bleeding in adults with ALL treated with asparaginase

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-03-24 DOI:10.1016/j.bvth.2025.100065

Joseph F. Mort , David Brighton , Benjamin Mautner , Eric Pierce , Farid Ghamsari , Cecily Allen , Darren D’Souza , Imari Patel , Justin Lawson , Clayton Jackson , Karin Abernathy , Bradley Yelvington , Ryan Miller , Bhagirathbhai Dholaria , Heather Wolfe , Jordan Infield , Susan C. Locke , Rory M. Shallis , Vu H. Duong , Daniel R. Reed , Firas El Chaer

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Abstract

The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the incorporation of pediatric-inspired regimens that contain PEGylated asparaginase (PEG-Asp). However, PEG-Asp administration is associated with an increased rate of thrombosis. Data regarding the benefits of antithrombin (AT) repletion and prophylactic anticoagulation in adults receiving PEG-Asp–based regimens are limited. We performed a retrospective study to evaluate the rates of induction thrombosis and bleeding among adults receiving ALL therapy containing Asp at 6 academic centers in the United States. Of 233 patients who met the inclusion criteria, 98.3% received PEG-Asp. Ninety-six patients (41.2%) had their AT levels monitored, 58 patients (24.9%) received AT repletion, and 41 patients (17.6%) received prophylactic anticoagulation. Thirty-two patients (13.7%) experienced thrombotic events, with half (53.1%) being line-associated thromboses. In multivariate analysis, the odds of thrombosis did not differ between patients who received AT monitoring, AT repletion, or prophylactic anticoagulation. The odds of thrombosis were 4 times higher for patients with peripherally inserted central catheters than for those with other types of central lines (odds ratio, 4.112; 95% confidence interval, 1.622-10.427; P = .01). Thrombotic risk did not differ based on age, cumulative Asp dose, type of steroid administered, or whether transfusions were performed. Bleeding occurred in 12 patients (5.2%), and major bleeding occurred in 8 patients (3.4%). The odds of bleeding did not increase in the patients who received prophylactic anticoagulation. Our study brings into question whether prophylactic AT repletion and anticoagulation are beneficial strategies for reducing PEG-Asp–associated thrombosis, and large randomized prospective studies are needed.

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用天冬酰胺酶治疗的成人ALL患者预防血栓和出血策略的现实世界分析

【摘要】急性淋巴细胞白血病（ALL）成年患者的预后随着含有聚乙二醇化天冬酰胺酶（PEG-Asp）的儿科启发方案的结合而改善。然而，PEG-Asp给药与血栓形成率增加有关。关于抗凝血酶（AT）补充和预防性抗凝在成人接受peg - asp为基础的方案的好处的数据是有限的。我们进行了一项回顾性研究，以评估在美国6个学术中心接受含Asp的ALL治疗的成人中诱导血栓和出血的发生率。在233例符合纳入标准的患者中，98.3%接受了PEG-Asp治疗。96例（41.2%）患者接受了AT水平监测，58例（24.9%）患者接受了AT补充，41例（17.6%）患者接受了预防性抗凝治疗。32名患者（13.7%）发生血栓事件，其中一半（53.1%）为系相关血栓。在多变量分析中，血栓形成的几率在接受AT监测、AT补充或预防性抗凝治疗的患者之间没有差异。外周插入中心导管患者血栓形成的几率是其他类型中心导管患者的4倍(优势比，4.112；95%置信区间为1.622-10.427；P = 0.01)。血栓形成风险不因年龄、累计剂量、类固醇类型或是否输血而有差异。出血12例（5.2%），大出血8例（3.4%）。在接受预防性抗凝治疗的患者中，出血的几率没有增加。我们的研究提出了预防性AT补充和抗凝是否是减少peg - asp相关血栓形成的有益策略的问题，并且需要进行大型随机前瞻性研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Vessels, Thrombosis & Hemostasis

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