肿瘤细胞治疗研究
英文原题：Low reticulocyte count at infusion is a risk factor for ICANS in CAR-T cell therapy.
Low reticulocyte count at infusion is a risk factor for ICANS in CAR-T cell therapy.
输注时网织红细胞计数这一简单血液学参数，可能有助于预测 ICANS 的发生，并指导基于风险优化的 CAR-T 细胞治疗管理。
靶向CD19的嵌合抗原受体（CAR）-T细胞疗法已显示出对B细胞恶性肿瘤的疗效。然而，它们经常引起免疫效应细胞相关神经毒性综合征（ICANS），这可能危及生命并需要重症监护。即使不严重，ICANS也可导致住院时间延长并限制治疗选择，尤其是对老年患者。尽管具有临床意义，但尚未确定可靠的ICANS早期预测标志物。
为了识别ICANS的风险因素，我们回顾性分析了2019年至2024年在京都大学医院接受tisagenlecleucel（tisa-cel）、lisocabtagene maraleucel（liso-cel）或axicabtagene ciloleucel（axi-cel）治疗的B细胞淋巴瘤患者。
在106例患者中，76例接受tisa-cel，22例接受liso-cel，8例接受axi-cel。输注时的中位年龄为63.5岁（四分位距，57-69）。8例患者（8%）有中枢神经系统（CNS）受累史。ICANS发生于17例患者（16%），均伴有既往细胞因子释放综合征（CRS）。随后发生ICANS的患者在输注时的网织红细胞计数显著较低（1.57 vs 2.80 104/ L，P < 0.01）。多因素分析确定输注时低网织红细胞计数（HR，3.67；95% CI，1.23-11.02；P = 0.02）、CNS受累史（HR 8.37；95% CI，3.04-23.04；P < 0.01）和axi-cel（HR，4.56；95% CI，1.88-11.09；P < 0.01）为独立危险因素。按输注时网织红细胞计数中位数（2.57 104/ L）分组的患者中，计数较低者的30天ICANS累积发生率显著更高（30天时为25.5% vs 7.8%；P = 0.018）。
INTRODUCTION: Chimeric antigen receptor (CAR)-T cell therapies targeting CD19 have shown efficacy against B-cell malignancies. However, they frequently cause immune effector cell-associated neurotoxicity syndrome (ICANS), which can be life-threatening and require intensive care. Even when it is not severe, ICANS can lead to prolonged hospitalization and limit treatment options, especially for elderly patients. Despite its clinical significance, a reliable, early predictive marker for ICANS has not been identified. METHODS: To identify risk factors for ICANS, we retrospectively analyzed B-cell lymphoma patients who received tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), or axicabtagene ciloleucel (axi-cel) at Kyoto University Hospital from 2019 to 2024. RESULTS: Among 106 patients, 76 received tisa-cel, 22 liso-cel, and eight axi-cel. Median age at infusion was 63.5 years (interquartile range, 57-69). Eight patients (8%) had a history of central nervous system (CNS) involvement. ICANS occurred in 17 patients (16%), all with prior cytokine-release syndrome (CRS). Reticulocyte counts at infusion were significantly lower in patients who subsequently developed ICANS (1.57 versus 2.80 104/ L, P < 0.01). Multivariate analysis identified a low reticulocyte count at infusion (HR, 3.67; 95% CI, 1.23-11.02; P = 0.02), history of CNS involvement (HR 8.37; 95% CI, 3.04-23.04; P < 0.01), and axi-cel (HR, 4.56; 95% CI, 1.88-11.09; P < 0.01) as independent risk factors. Patients divided by the median reticulocyte count at infusion (2.57 104/ L) demonstrated significantly higher 30-day cumulative incidence of ICANS in those with lower counts (25.5% versus 7.8% at 30 days; P = 0.018). CONCLUSION: Reticulocyte counts at infusion, a simple hematological parameter, may help predict ICANS development and guide optimal risk-based management of chimeric antigen receptor (CAR)-T cell therapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
