接受抗cd19嵌合抗原受体(CAR) t细胞治疗的急性b细胞白血病年轻成人和儿童的不良事件管理

IF 2.3 Q2 HEMATOLOGY Blood Research Pub Date : 2023-04-30 DOI:10.5045/br.2023.2023026
Jae Won Yoo
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引用次数: 1

摘要

随着靶向CD19的免疫效应细胞疗法取得令人印象深刻的临床进展,嵌合抗原受体(CAR) t细胞疗法已成为治疗复发/难治性b细胞恶性肿瘤的新范例。目前,已经批准了三种第二代CAR - t细胞疗法,其中只有tisagenlecleucel(组织细胞)被批准用于治疗b细胞急性淋巴细胞白血病(ALL)的儿童和年轻人,持久缓解率约为60-90%。尽管CAR - t细胞疗法被认为可以治疗难治性B-ALL,但它们具有独特的毒性,如细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)。CAR - t细胞疗法毒性的严重程度可以根据几个临床因素而变化。在极少数情况下,严重的CRS可发展为暴发性高炎症综合征,即噬血细胞性淋巴组织细胞增多症,预后较差。CRS/ICANS的一线治疗包括托珠单抗和皮质类固醇。当严重的CAR - t细胞毒性对一线治疗产生耐药性时,需要一种额外的方法来控制持续的炎症。除了CRS/ICANS之外,CAR - t细胞疗法还可能导致早期和延迟的血液毒性,这可能使患者易受严重感染。生长因子和抗感染预防的使用应根据患者特定的危险因素遵循机构指南。这篇综述全面总结了最新的实用建议,用于处理成人和儿童抗cd19 CAR - t细胞治疗后的急性和延迟不良反应。
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Management of adverse events in young adults and children with acute B-cell lymphoblastic leukemia receiving anti-CD19 chimeric antigen receptor (CAR) T-cell therapy.

With impressive clinical advancements in immune effector cell therapies targeting CD19, chimeric antigen receptor (CAR) T-cell therapy has emerged as a new paradigm for treating relapsed/refractory B-cell malignancies. Currently, three second-generation CAR T-cell therapies have been approved, of which only tisagenlecleucel (tisa-cel) is approved for treating children and young adults with B-cell acute lymphoblastic leukemia (ALL) with durable remission rates of approximately 60‒90%. Although CAR T-cell therapies are considered to treat refractory B-ALL, they are associated with unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The severity of CAR T-cell therapy toxicities can vary according to several clinical factors. In rare cases, severe CRS can progress to a fulminant hyperinflammatory syndrome known as hemophagocytic lymphohistiocytosis, which has a poor prognosis. The first-line treatments for CRS/ICANS include tocilizumab and corticosteroids. When severe CAR T-cell toxicity is resistant to first-line treatment, an additional approach is required to manage the persistent inflammation. In addition to CRS/ICANS, CAR T-cell therapy can cause early and delayed hematological toxicity, which can predispose patients to severe infections. The use of growth factors and anti-infective prophylaxis should follow institutional guidelines according to patient-specific risk factors. This review provides a thorough summary of updated practical recommendations for managing acute and delayed adverse effects following anti-CD19 CAR T-cell therapy in adults and children.

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来源期刊
Blood Research
Blood Research HEMATOLOGY-
CiteScore
3.70
自引率
0.00%
发文量
64
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