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CAR-T细胞疗法后新发严重血细胞减少症:76例复发或难治性急性淋巴细胞白血病患者的分析

New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia.

作者信息

Wang Linqin, Hong Ruimin, Zhou Linghui, Ni Fang, Zhang Mingming, Zhao Houli, Wu Wenjun, Wang Yiyun, Ding Shuyi, Chang Alex H, Hu Yongxian, Huang He

机构信息

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Institute of Hematology, Zhejiang University, Hangzhou, China.

出版信息

Front Oncol. 2021 Jun 30;11:702644. doi: 10.3389/fonc.2021.702644. eCollection 2021.

Abstract

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.

摘要

尽管嵌合抗原受体T(CAR-T)细胞疗法已被证明在治疗复发或难治性B细胞血液系统恶性肿瘤方面有效,但严重的血液学毒性仍然是一个棘手的问题。这项回顾性研究评估了76例复发/难治性急性淋巴细胞白血病患者在接受CAR-T细胞输注后新发严重血细胞减少的特征和危险因素。新发严重血细胞减少的发生率很高,包括严重中性粒细胞减少(SN)(39/56,70%)、严重贫血(SA)(35/66,53%)和严重血小板减少(ST)(31/64,48%)。相比之下,细胞因子释放综合征(CRS)分级较高的队列中,严重血细胞减少的发生率更高,持续时间更长。多变量分析显示,最大(max)lg D-二聚体升高和CRS峰值时间延迟是SN恢复的独立危险因素;max lg IL-10升高和CRS恢复延迟是SA的危险因素;max lg铁蛋白水平高是ST的危险因素;CRS发作或恢复时间较长以及CRS分级较高是血液学毒性延长的危险因素。这些观察结果得出结论,CRS的特征,包括其持续时间、严重程度和血清标志物,与新发严重血细胞减少的发生率和恢复相关,提示对CAR-T治疗后严重血细胞减少进行临床干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ce/8278328/0c222d61beb7/fonc-11-702644-g001.jpg

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