最近的证据揭示了克隆造血（CH）和为治疗血液恶性肿瘤而建立的细胞疗法之间的重要相互作用。 CH 对嵌合抗原受体 (CAR) T 细胞疗法的安全性、有效性和结果的影响目前正在研究中。我们分析了 110 名复发/难治性 B 细胞非霍奇金淋巴瘤 (n = 105) 或急性淋巴细胞白血病 (ALL) (n = 5) 患者，接受 Axicabtagene-Ciloleucel (39%)、Tisagenlecleucel (51%) 或Brexucabtagene autoleucel (10%)。使用纠错靶向测序，检测到 CAR T 细胞输注时 CH 患病率高达 56.4%（变异等位基因频率 [VAF] ≥1%）。最常见的突变基因是 PPM1D，其次是 DNMT3A、TET2、ASXL1 和 TP53。与单核细胞和粒细胞相比，B 细胞和 T 细胞中的变异等位基因频率显着较低。 CH 不会增加 CAR T 相关毒性的风险。无论克隆大小、年龄或 CAR T 产品如何，CHpos 和 CHneg 患者中细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的发生率相似。长期血细胞减少与 CH 无关。 CHpos 患者的最佳总体缓解率 (ORR) 在数值上较高，但并未显着较高（ORR 76.7% 对比 62.2%；P = 0.13）。此外，CH 状态不能预测无进展生存期或总生存期。最后，序贯分析显示 VAF 适度增加 1.3%，并在输注后 100 天内获得新突变。 CH 在接受 CAR T 细胞的大 B 细胞淋巴瘤/ALL 患者中很常见，但不影响毒性、治疗反应或结果。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 代表欧洲血液学协会出版。

Recent evidence revealed important interactions between clonal hematopoiesis (CH) and cellular therapies established for the treatment of hematologic malignancies. The impact of CH on safety, efficacy, and outcome of chimeric antigen receptor (CAR) T-cell therapy is currently under investigation. We analyzed 110 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (n = 105) or acute lymphoblastic leukemia (ALL) (n = 5), treated with Axicabtagene-Ciloleucel (39%), Tisagenlecleucel (51%), or Brexucabtagene autoleucel (10%). Using error-corrected targeted sequencing, a high CH prevalence of 56.4% (variant allele frequency [VAF] ≥1%) at the time of CAR T-cell infusion was detected. The most frequently mutated gene was PPM1D followed by DNMT3A, TET2, ASXL1, and TP53. Variant allele frequencies were significantly lower in B and T cells compared with monocytes and granulocytes. CH did not increase the risk of CAR T-related toxicities. The incidences of cytokine release syndrome and immune effector-cell-associated neurotoxicity syndrome were similar between CHpos and CHneg patients, regardless of clone size, age, or CAR T product. Prolonged cytopenias were not associated with CH. Best overall response rates (ORRs) were numerically but not significantly higher in CHpos patients (ORR 76.7% versus 62.2%; P = 0.13). Furthermore, CH status did not predict progression-free survival or overall survival. Lastly, sequential analysis showed a modest VAF increase of 1.3% and acquisition of novel mutations within 100 days postinfusion. CH was frequent in large B-cell lymphoma/ALL patients receiving CAR T-cells but did not affect toxicity nor treatment response or outcome.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.