肿瘤细胞治疗研究
英文原题：SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101).
这些数据支持在异基因HCT、自体HCT和CAR-T细胞治疗后三至四个月开始接种mRNA SARS-CoV-2疫苗。
细胞治疗后接种SARS-CoV-2疫苗的最佳时机尚不完全清楚。
描述在细胞治疗后<4个月与4-12个月启动SARS-CoV-2疫苗接种后的体液和细胞反应。
多中心前瞻性观察性研究。美国34个中心。2021年4月至2022年6月期间入组的466名异基因造血细胞移植（HCT；n=231）、自体HCT（n=170）或CAR-T 细胞（CAR-T细胞）治疗（n=65）接受者。干预措施：作为常规护理一部分的SARS-CoV-2疫苗接种。测量指标：我们在疫苗接种前和接种后最多五个时间点获取血液，并在所有参与者中检测SARS-CoV-2刺突（anti-S）IgG，以及在亚组中检测针对Wuhan D614G、Delta B.1.617.2和Omicron B.1.1.529株的中和抗体，以及SARS-CoV-2特异性T细胞受体（TCR）。
抗S IgG和中和抗体反应在HCT受者中随疫苗接种而增加，与疫苗启动时机无关，但在4个月内启动疫苗的CAR-T细胞受者中未发生变化。抗S IgG 2,500 U/mL与高中和抗体滴度相关，在异基因HCT、自体HCT和CAR-T细胞受者中分别有70%、69%和34%在最后一个时间点达到该水平。SARS-CoV-2特异性T细胞反应分别在57%、83%和58%的受者中达到。在细胞治疗后<4个月与4-12个月启动疫苗接种的参与者中，体液和细胞反应无显著差异。细胞治疗前SARS-CoV-2感染或疫苗接种是细胞治疗后抗S IgG水平的关键预测因素。局限性：大多数参与者为成年人，且接种的是mRNA疫苗。
BACKGROUND: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. OBJECTIVE: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy. DESIGN: Multicenter prospective observational study. SETTING: 34 centers in the United States. PARTICIPANTS: 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022. INTERVENTIONS: SARS-CoV-2 vaccination as part of routine care. MEASUREMENTS: We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. RESULTS: Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG 2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels. LIMITATIONS: The majority of participants were adults and received mRNA vaccines. CONCLUSIONS: These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy. FUNDING: National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.
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