决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.
通过概率机器学习图模型,我们在一个包含多种血液疾病患者的大型队列(n=1166)中,估计了接种SARS-CoV-2疫苗后3-6周时可检测到抗SARS-CoV-2抗体的条件概率。
既往对血液系统疾病患者完成SARS-CoV-2全程疫苗接种后抗体应答的研究,确认其抗体水平低于一般人群。血液病患者的血清学应答因疾病类型及状态、治疗方式以及治疗与接种的时间关系而差异很大。本研究利用概率图模型估算大型血液病患者队列(n=1,166)接种SARS-CoV-2疫苗后3至6周可检测到抗SARS-CoV-2抗体的条件概率。多数患者接种mRNA疫苗(97%),主要为Moderna mRNA-1273(74%),其次为Pfizer-BioNTech BNT162b2(23%)。全队列完成全程接种后3至6周抗体总体检出率为79%。疾病类型、抗CD20单克隆抗体治疗与接种间隔、年龄、糖皮质激素治疗、疫苗种类、疾病状态及既往SARS-CoV-2感染等,是影响SARS-CoV-2反应性IgG抗体检出的重要因素。接种前6个月内接受抗CD20单抗治疗的B细胞非霍奇金淋巴瘤患者抗体检出概率较低(29.32%);年轻慢性骨髓增殖性肿瘤患者最高(99.53%)。在所有情境中,Moderna mRNA-1273疫苗的抗体检出概率较高。本研究描绘了全队列及B细胞NHL、慢性淋巴细胞白血病(CLL)、多发性骨髓瘤(MM)和慢性骨髓增殖性肿瘤等特定情境下可检测抗体的条件概率,有助于制定针对这些重度免疫抑制患者的额外预防和/或监测措施。
Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna mRNA-1273 (74%) followed by Pfizer-BioNTech BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.
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