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嵌合抗原受体 T 细胞治疗后淋巴瘤患者预免疫抗体滴度的连续评估。

Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.

机构信息

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota.

出版信息

Transplant Cell Ther. 2024 Apr;30(4):455.e1-455.e7. doi: 10.1016/j.jtct.2024.02.003. Epub 2024 Feb 10.

Abstract

Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester. In our cohort of 95 CAR-T recipients, almost one-half had low CD4 T and B cell counts prior to CAR-T that remained persistently low post-CAR-T. Prior to CAR-T, the seronegative rate was lowest for tetanus and highest for pneumococcus irrespective of prior transplantation status (within 2 years of CAR-T). At 3 months post-CAR-T, overall seronegativity rates were similar to pre-CAR-T rates for the prior transplantation and no prior transplantation groups. For patients who received IVIG, loss of seropositivity was seen for hepatitis A (1 of 7; 14%). No seroconversion was noted for pneumococcus. For patients who did not receive IVIG, loss of seropositivity was seen for pneumococcus (2 of 5; 40%) and hepatitis A (1 of 4; 25%). CAR-T recipients commonly experience T cell and B cell lymphopenia and might not have adequate antibody titers against vaccine-preventable diseases despite IVIG supplementation. Loss of antibody titers post-CAR-T is possible, highlighting the need for revaccination. Additional studies with long-term follow-up are needed to inform the optimal timing of immunization post-CAR-T.

摘要

嵌合抗原受体 T 细胞治疗 (CAR-T) 受者的抗体滴度和免疫接种的潜在需求尚未经过正式研究。先前的研究表明,CD19 靶向 CAR-T 可诱导持续的 B 细胞发育不全,但保留浆细胞以产生体液免疫反应。为了评估 CAR-T 受者的免疫受体库和抗体滴度状态,我们对梅奥诊所罗切斯特院区接受抗 CD19 CAR-T 的患者进行了一项免疫细胞恢复和疫苗抗体滴度的回顾性研究。在我们的 95 名 CAR-T 受者队列中,近一半在接受 CAR-T 前 CD4 T 和 B 细胞计数较低,CAR-T 后持续较低。在接受 CAR-T 之前,破伤风的血清阴性率最低,肺炎球菌的血清阴性率最高,与既往移植状态无关(在 CAR-T 前 2 年内)。在 CAR-T 后 3 个月,总体血清阴性率与既往移植组和无既往移植组的 CAR-T 前比率相似。对于接受 IVIG 的患者,甲型肝炎的血清阳性率下降(7 例中有 1 例;14%)。肺炎球菌未出现血清转化率。对于未接受 IVIG 的患者,肺炎球菌(5 例中有 2 例;40%)和甲型肝炎(4 例中有 1 例;25%)的血清阳性率下降。CAR-T 受者通常经历 T 细胞和 B 细胞淋巴细胞减少症,尽管补充 IVIG,但可能对疫苗可预防疾病没有足够的抗体滴度。CAR-T 后抗体滴度下降可能存在,强调需要重新接种疫苗。需要进行长期随访的进一步研究,以确定 CAR-T 后免疫接种的最佳时机。

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