Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain.
Paediatric Intensive Care Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Front Immunol. 2023 Aug 2;14:1219289. doi: 10.3389/fimmu.2023.1219289. eCollection 2023.
Chimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients.
Prospective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality.
CAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344).
PICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.
嵌合抗原受体 (CAR) T 细胞 CD19 疗法是治疗复发/难治性 B 细胞急性淋巴细胞白血病的有效方法。它可能会导致危及生命的毒性，这通常需要入住儿科重症监护病房 (PICU)。目的：描述这些患者的临床特征、治疗和结局。
这是一项在 2016 年至 2021 年期间在一家三级儿科医院进行的前瞻性观察队列研究。纳入接受 CAR-T 输注后入住 PICU 的患儿。我们收集了流行病学、临床特征、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)、治疗、住院时间和死亡率。
共输注了 59 例 CAR-T 细胞（4-1BB 构建体）。24 例（40.7%）需要入住 PICU，住院时间为 4 天（IQR 3-6）。中位年龄为 8.3 岁（范围 4-24）。入住 PICU 的患者在输注前的疾病负担更高：骨髓中 24%的原始细胞（IQR 5-72）vs. 0（0-6.9），p<0.001。无 <5%原始细胞的患者入住 PICU。入住 PICU 的主要原因是 CRS（n=20，83.3%）和 ICANS（n=3，12.5%）。14 例患者（58.3%）需要正性肌力支持，14 例（58.3%）需要呼吸支持。16 例患者（66.6%）接受了托珠单抗治疗，10 例（41.6%）接受了皮质类固醇治疗，6 例（25.0%）接受了阿那白滞素治疗，5 例（20.8%）接受了西妥昔单抗治疗。10 例患者（41.6%）出现神经毒性，其中 6 例为严重神经毒性（ICANS 3-4）。2 例患者（8.3%）因难治性 CRS-噬血细胞性淋巴组织细胞增生症（carHLH）而在 PICU 死亡。在需要入住 PICU 的患者中，CAR-T 治疗后的复发率没有显著差异，CD19 阴性的患者更常见（p=0.344）。
CAR-T 治疗后入住 PICU 主要是由于 CRS。支持治疗可有效管理并提高生存率。一些 carHLH 患者可能会出现暴发性病程。
