Zandaki Dua'a, Selukar Subodh, Bi Yu, Li Ying, Zinsky Megan, Bonifant Challice L, Epperly Rebecca, Keerthi Dinesh, Triplett Brandon M, Gottschalk Stephen, Naik Swati, Talleur Aimee C
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.
Blood Adv. 2025 Jan 28;9(2):270-279. doi: 10.1182/bloodadvances.2024014027.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are complications of CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy. The Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) scores have been retrospectively proven to be predictive of CRS and ICANS in adult CAR T-cell recipients. However, these scores have not been evaluated in pediatric cohorts. We retrospectively report on 76 pediatric and adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with CD19-CAR T cells at St. Jude Children's Research Hospital or Johns Hopkins Hospital. Data included patient, disease, and treatment characteristics. EASIX and m-EASIX scores were calculated at days -5 before, 0, and +3 after CAR T-cell infusion. CRS and ICANS occurred in 47 and 17 patients, respectively. At all evaluated time points, the median EASIX scores were higher for patients who developed severe CRS and any grade ICANS, and the median m-EASIX scores were higher in patients who developed severe CRS and severe ICANS than those with no/mild CRS/ICANS. Receiver operating characteristic curve analysis showed that both scores were strong predictors of CRS, especially severe CRS, at all time points. Any grade and severe ICANS were best predicted by both scores at day +3. m-EASIX uniformly outperformed EASIX, except for predicting any grade ICANS. Our results validate the potential utility of EASIX and m-EASIX scores for predicting CAR T-cell-related complications for pediatric and AYA patients.
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）是靶向CD19的嵌合抗原受体（CD19-CAR）T细胞疗法的并发症。内皮激活和应激指数（EASIX）及改良EASIX（m-EASIX）评分已通过回顾性研究证明可预测成年CAR T细胞接受者发生CRS和ICANS的风险。然而，这些评分尚未在儿科队列中进行评估。我们回顾性报告了在圣裘德儿童研究医院或约翰霍普金斯医院接受CD19-CAR T细胞治疗的76例复发/难治性B细胞急性淋巴细胞白血病的儿科、青少年及青年成人（AYA）患者。数据包括患者、疾病和治疗特征。在CAR T细胞输注前第-5天、第0天和输注后第+3天计算EASIX和m-EASIX评分。分别有47例和17例患者发生了CRS和ICANS。在所有评估时间点，发生严重CRS和任何级别的ICANS的患者的EASIX评分中位数更高，发生严重CRS和严重ICANS的患者的m-EASIX评分中位数高于未发生/轻度CRS/ICANS的患者。受试者工作特征曲线分析表明，在所有时间点，这两个评分都是CRS尤其是严重CRS的强有力预测指标。在第+3天，这两个评分对任何级别和严重ICANS的预测效果最佳。除了预测任何级别的ICANS外，m-EASIX的表现均优于EASIX。我们的结果验证了EASIX和m-EASIX评分在预测儿科及AYA患者CAR T细胞相关并发症方面的潜在效用。
