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托珠单抗用于治疗难治性爱泼斯坦-巴尔病毒阳性弥漫性大B细胞淋巴瘤患者单倍体相合供者移植后严重细胞因子释放综合征。

Tocilizumab for severe cytokine-release syndrome after haploidentical donor transplantation in a patient with refractory Epstein-Barr virus-positive diffuse large B-cell lymphoma.

作者信息

Ureshino Hiroshi, Ando Toshihiko, Kizuka Haruna, Kusaba Kana, Sano Haruhiko, Nishioka Atsujiro, Itamura Hidekazu, Shindo Takero, Kubota Yasushi, Kojima Kensuke, Kimura Shinya

机构信息

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

出版信息

Hematol Oncol. 2018 Feb;36(1):324-327. doi: 10.1002/hon.2481. Epub 2017 Oct 3.

DOI:10.1002/hon.2481
PMID:28971493
Abstract

It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT. A 46-year-old man was diagnosed with haemophagocytic syndrome associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Salvage chemotherapy was unsuccessful; consequently, he received haplo-HCT. On day +4, he developed grade 3 CRS, subsequently high-dose corticosteroid initiated. Nevertheless, on day +6, he developed grade 4 CRS, resulting in requirement for ventilator support and multiple vasopressors. Corticosteroid could not improve severe CRS; therefore, tocilizumab was administered on day +14. Serum C-reactive protein level transiently decreased and weaned multiple vasopressors. Although CRS improved, he developed candidaemia; consequently, he died on day +34. Tocilizumab could transiently improve severe CRS after haplo-HCT. Although tocilizumab may have led to the improvement of CRS, a remaining concern is whether it inhibited the patient's ability to mount antifungal immunity, leading to their demise.

摘要

已有充分文献记载,患者在使用单克隆抗体(如嵌合抗原受体修饰的T细胞)后可能会发生细胞因子释放综合征(CRS)。细胞因子释放综合征是接受单倍体相合供者异基因造血细胞移植(haplo-HCT)患者的常见并发症。虽然haplo-HCT后的严重CRS是一种潜在的危及生命的毒性反应,但尚未确立标准治疗方法。使用抗IL-6受体抗体托珠单抗进行细胞因子阻断,已被证明对嵌合抗原受体修饰的T细胞治疗后发生CRS的患者有效,也改善了haplo-HCT后的CRS。一名46岁男性被诊断为与爱泼斯坦-巴尔病毒阳性弥漫性大B细胞淋巴瘤相关的噬血细胞综合征。挽救性化疗未成功;因此,他接受了haplo-HCT。在+4天,他出现了3级CRS,随后开始使用大剂量皮质类固醇。然而,在+6天,他发展为4级CRS,导致需要呼吸机支持和多种血管升压药。皮质类固醇无法改善严重的CRS;因此,在+14天给予托珠单抗。血清C反应蛋白水平短暂下降,多种血管升压药停用。虽然CRS有所改善,但他发生了念珠菌血症;因此,他在+34天死亡。托珠单抗可短暂改善haplo-HCT后的严重CRS。虽然托珠单抗可能导致了CRS的改善,但一个仍然存在的担忧是它是否抑制了患者产生抗真菌免疫的能力,从而导致了他们的死亡。

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