CD19-positive acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (B-ALL) have a dismal prognosis when first-line therapy fails [1, 2]. Complete responses in relapsed/refractory (R/R) B-ALL to second-line therapy are 30–45%, with a median overall survival (OS) of only 5–8 months, and is even lower after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [2]. The response rate in R/R diffuse large B-cell lymphoma (DLBCL) is approximately 40% to first-line therapy, and only 15–20% achieve sustained response to autologous HSCT (auto-HSCT) [1]. Chimeric antigen receptor (CAR)-T cells anti-CD19 emerged as a potential curative therapy for B-cell malignancies that failed to standard ones, with response rates up to 80% of R/R B-ALL and DLBCL, superior to conventional therapies [3,4,5,6]. However, commercial CAR-T cell products are expensive [7], fostering alternative CAR-T manufacturing [8, 9]. We report the outcomes in 20 R/R B-NHL or B-ALL patients treated with academic CD19-directed CAR-T cell products.

This is a two-center (Hospital das Clínicas de Ribeirão Preto and Hospital das Clínicas de São Paulo, University of São Paulo) retrospective report on the efficacy and safety of an academic CD19-directed CAR-T cell product (HD37 clone; 4-1BB as costimulatory domain) for patients with R/R B-NHL or B-ALL, treated between 2019 and 2023. Lymphocytes were harvested by apheresis. Afterward, the apheresis products underwent cell selection, activation, transduction, and expansion before cryopreservation. On day zero, CAR-T cell products were thawed and infused after lymphodepletion. We evaluated the incidence and severity of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, coagulopathy, and hypogammaglobulinemia, and response rate, defined as complete response (CR) or partial response (PR) (B-NHL) or undetected leukemic blasts (B-ALL) on days 30 and 90 after cell infusion. Results were expressed as median (range) and categorical variables as percent. This report was approved by the local Research Ethics Committee (Methods details in Supplementary Material).

当一线治疗失败时，CD19 阳性急性淋巴细胞白血病 (B-ALL) 和非霍奇金淋巴瘤 (B-ALL) 的预后较差 [1, 2]。复发/难治性 (R/R) B-ALL 对二线治疗的完全缓解率为 30-45%，中位总生存期 (OS) 仅 5-8 个月，异基因造血干细胞移植后更低（异基因造血干细胞移植）[2]。 R/R 弥漫性大 B 细胞淋巴瘤 (DLBCL) 一线治疗的缓解率约为 40%，只有 15-20% 对自体 HSCT (auto-HSCT) 实现持续缓解 [1]。嵌合抗原受体 (CAR)-T 细胞抗 CD19 成为治疗标准疗法失败的 B 细胞恶性肿瘤的潜在疗法，对 R/R B-ALL 和 DLBCL 的缓解率高达 80%，优于传统疗法[3,4,5,6]。然而，商业 CAR-T 细胞产品价格昂贵 [7]，促进了替代性 CAR-T 制造 [8, 9]。我们报告了 20 名接受学术 CD19 定向 CAR-T 细胞产品治疗的 R/R B-NHL 或 B-ALL 患者的结果。

这是两个中心（Hospital das Clínicas de Ribeirão Preto 和 Hospital das Clínicas de São Paulo、圣保罗大学）关于学术 CD19 定向 CAR-T 细胞产品（HD37 克隆；4- 1BB 作为共刺激结构域），适用于 2019 年至 2023 年间接受治疗的 R/R B-NHL 或 B-ALL 患者。通过单采术收集淋巴细胞。随后，单采产物经过细胞选择、激活、转导和扩增，然后冷冻保存。第 0 天，CAR-T 细胞产品在淋巴细胞清除后解冻并输注。我们评估了不良事件 (AE) 的发生率和严重程度，例如细胞因子释放综合征 (CRS)、免疫效应细胞相关神经毒性综合征 (ICANS)、血细胞减少症、凝血病和低丙种球蛋白血症，以及缓解率，定义为完全缓解 (CR ）或部分缓解（PR）（B-NHL）或细胞输注后第 30 天和 90 天未检测到的白血病母细胞（B-ALL）。结果以中位数（范围）表示，分类变量以百分比表示。该报告得到了当地研究伦理委员会的批准（补充材料中的方法详细信息）。