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开发和验证一种自动计算方法,以评估免疫效应细胞相关血液毒性的程度。

Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity.

机构信息

Fred Hutchinson Cancer Center, Seattle, WA, USA.

University of Washington, Seattle, WA, USA.

出版信息

Bone Marrow Transplant. 2024 Jul;59(7):910-917. doi: 10.1038/s41409-024-02278-3. Epub 2024 Apr 16.

Abstract

Hematologic toxicity frequently complicates chimeric antigen receptor (CAR) T-cell therapy, resulting in significant morbidity and mortality. In an effort to standardize reporting, the European Hematology Association (EHA) and European Society of Blood and Marrow Transplantation (EBMT) devised the immune effector cell-associated hematotoxicity (ICAHT) grading system, distinguishing between early (day 0-30) and late (after day +30) events based on neutropenia depth and duration. However, manual implementation of ICAHT grading criteria is time-consuming and susceptible to subjectivity and error. To address these challenges, we introduce a novel computational approach, utilizing the R programming language, to automate early and late ICAHT grading. Given the complexities of early ICAHT grading, we benchmarked our approach both manually and computationally in two independent cohorts totaling 1251 patients. Our computational approach offers significant implications by streamlining grading processes, reducing manual time and effort, and promoting standardization across varied clinical settings. We provide this tool to the scientific community alongside a comprehensive implementation guide, fostering its widespread adoption and enhancing reporting consistency for ICAHT.

摘要

血液学毒性经常使嵌合抗原受体 (CAR) T 细胞疗法复杂化,导致发病率和死亡率显著增加。为了实现报告的标准化,欧洲血液学协会 (EHA) 和欧洲血液与骨髓移植学会 (EBMT) 设计了免疫效应细胞相关血液毒性 (ICAHT) 分级系统,根据中性粒细胞减少的深度和持续时间,区分早期 (第 0-30 天) 和晚期 (第 +30 天后) 事件。然而,手动实施 ICAHT 分级标准既耗时又容易受到主观性和误差的影响。为了解决这些挑战,我们引入了一种新的计算方法,利用 R 编程语言实现早期和晚期 ICAHT 分级的自动化。考虑到早期 ICAHT 分级的复杂性,我们在两个独立的队列中分别进行了手动和计算基准测试,共涉及 1251 名患者。我们的计算方法具有重要意义,通过简化分级过程、减少手动时间和工作量,并促进在不同临床环境下的标准化,从而提高了效率。我们提供了这个工具以及一个全面的实施指南给科学界,促进其广泛采用,并提高 ICAHT 的报告一致性。

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