CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy.
Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy.
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嵌合抗原受体(CAR)T细胞疗法改善了复发和/或难治性大B细胞淋巴瘤(r/r LBCL)的结局。然而,其脱靶效应导致严重的持续性体液免疫缺陷。巨细胞病毒(CMV)是一种潜伏病毒,在免疫抑制患者中可能危及生命。在CAR-T 细胞治疗背景下,亚洲人种是临床显著CMV感染的危险因素。
然而,CAR-T 细胞疗法对日本患者CMV再激活的影响仍不清楚。既往报道使用聚合酶链反应(PCR),但我们使用pp65抗原血症试验回顾性研究了r/r LBCL患者的长期影响。
该研究纳入46例患者。9例(19.6%)发生CMV再激活,中位发生时间为13天。其中6例患者接受了抢先治疗,无一例发生CMV终末器官疾病。原发难治性疾病、2-4级细胞因子释放综合征和高剂量皮质类固醇是CMV再激活的危险因素。长期随访显示,CMV再激活很少在输注后28天之后发生。
我们使用pp65抗原血症试验的研究显示,CMV再激活的发生率、发生时间和危险因素与既往使用PCR的报道相似。
Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL).
However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection.
However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19. 6%) developed CMV reactivation, with a median onset of 13 days.
Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2-4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion.
Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR.
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