Marschollek Paweł, Liszka Karolina, Mielcarek-Siedziuk Monika, Dachowska-Kałwak Iwona, Haze Natalia, Panasiuk Anna, Olejnik Igor, Jarmoliński Tomasz, Frączkiewicz Jowita, Gamrot Zuzanna, Radajewska Anna, Bil-Lula Iwona, Kałwak Krzysztof
Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
Division of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Biomedicines. 2024 Jul 21;12(7):1622. doi: 10.3390/biomedicines12071622.
CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.
靶向CD19的嵌合抗原受体T细胞（CAR-T）疗法彻底改变了复发/难治性（r/r）前体B细胞急性淋巴细胞白血病（ALL）的治疗方式。然而，它可能与免疫激活相关的急性毒性反应有关，尤其是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）。活化免疫细胞释放的细胞因子在其病理生理学中起关键作用。本研究对接受替沙格宁（tisagenlecleucel）治疗的儿童的促炎蛋白和细胞因子进行了前瞻性分析。在治疗前以及输注后的连续几天对C反应蛋白、纤维蛋白原、铁蛋白、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、干扰素γ（IFNγ）和肿瘤坏死因子α（TNFα）进行了系列测量。CRS的发生率为77.8%，ICANS的发生率为11.1%。未观察到≥3级的CRS。所有并发症均发生在输注后14天内。在CRS≥2级的儿童中发现了更高的生物标志物浓度。它们的水平与疾病负担和CAR-T细胞剂量相关。虽然细胞因子释放综合征很常见，但大多数病例为轻度，主要是由于淋巴细胞清除化疗（LDC）前疾病负担较低。ICANS的发生频率较低，但表现出不同的临床病程。所有毒性反应均非致命。所有分析的生物标志物在CAR-T输注后14天内升高，大多数在输注后第三天左右达到峰值。
