CAR T cell therapy in advanced B-ALL with heavy disease burden

Immunomedicine Pub Date : 2022-07-17 DOI:10.1002/imed.1037
Kaiting Tang BS, Zhuojun Ling MD, Jing Pan MDPhD, He Huang MDPhD
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Abstract

In recent years, CD19-directed chimeric antigen receptor (CAR) T cell therapy has exhibited significant potency for treating pediatric relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Nonetheless, many patients with disease progressing rapidly may not benefit from this therapy. Actually, 10%–20% of these patients with rapidly progressive disease failed in CAR T cell manufacturing. Besides, some patients died of disease progression earlier than CAR T cells expanding in vivo. How to deal with the fast progressive disease and ensure successful manufacturing and expansion of CAR T cells are still very important questions for the clinicians. In this brief report, some clinical experience to handle these tough situations in our center will be introduced. Bridging chemotherapy and post-CAR antitumor managements help to control progressive blasts and contribute to the success of CAR T cell therapy. The optimal timing of apheresis and adjusted protocol for manufacturing CAR T cells are critical for advanced patients. Optimal treatment options and how they should be applied to advanced B-ALL with heavy disease burden still need to be discussed.

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CAR - T细胞治疗加重疾病负担的晚期B-ALL
近年来,cd19靶向嵌合抗原受体(CAR) T细胞疗法在治疗儿童复发或难治性b细胞急性淋巴细胞白血病(r/r B-ALL)方面显示出显著的效力。然而,许多疾病进展迅速的患者可能无法从这种治疗中获益。实际上,这些快速进展的疾病患者中有10%-20%在CAR - T细胞制造中失败。此外,一些患者早于CAR - T细胞在体内扩增就死于疾病进展。如何应对这种快速发展的疾病,并确保CAR - T细胞的成功制造和扩增仍然是临床医生面临的非常重要的问题。在这篇简短的报告中,我将介绍我中心处理这些棘手情况的一些临床经验。桥接化疗和CAR - T后抗肿瘤管理有助于控制进展性母细胞,有助于CAR - T细胞治疗的成功。对于晚期患者来说,最佳的分离时间和制造CAR - T细胞的调整方案至关重要。对于疾病负担沉重的晚期B-ALL,最佳治疗方案及如何应用仍需讨论。
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