为了成功地实施嵌合抗原受体T细胞（CAR-T）治疗，必须有效生产CAR-T细胞，而不受亚最优扩增导致的失败影响。为了确定CAR-T细胞制造失败的风险因素，我们在日本进行了一项全国队列研究，并分析了接受tisagenlecleucel生产的弥漫性大B细胞淋巴瘤（DLBCL）患者。我们比较了30例失败组（占7.4%）和成功组（n = 378）的临床因素。在失败组中，已用苯达莫司汀治疗的患者比例（43.3％vs14.8％；p <0.001）明显较高，其外周血小板计数（12.0 vs. 17.0×104 /μL；p = 0.01）和CD4 / CD8 T细胞比例（0.30 vs. 0.56； p＜0.01）明显较低。多元分析表明，接受较短间隔洗脱期的苯达莫司汀重复使用（OR，5.52；p = 0.013，6个周期及以上，间隔期为3-24个月；OR，57.09；p = 0.005，3个周期及以上，间隔期＜3个月），外周血小板计数低（每105 /μL的OR，0.495；p = 0.022）或外周血CD4 / CD8比例低（＜三分之一的OR，3.249；p = 0.011）将增加制造失败的风险。制造失败仍是DLBCL患者CAR-T细胞治疗的障碍。避免重复使用苯达莫司汀且没有充分洗脱等风险因素，以及风险适应的策略可能有助于优化DLBCL患者CAR-T细胞疗法。©2023 The Authors。英国血液学杂志由英国血液学会和约翰·威利·琼斯有限公司出版。

For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 104 /μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3-24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105 /μL; p = 0.022) or low CD4/CD8 ratios (