在CD19 CAR T-细胞疗法后的侵袭性淋巴瘤
Guido Kobbe1, Monika Brüggemann1, Ben-Niklas Baermann1
1From the Department of Hematology, Oncology and Clinical Immunology (G.K., B.-N.B., P.-M.B., N.L., A.R., M. Seifert, C.S., U.G., R.-P.C., K.N., P.J., T.U., S.D.), the Institute of Pathology (M. Seidel, I.E.), the Institute for Transplantation Diagnostics and Cellular Therapy (J.C.F., J.M.R.), the Departments of Nuclear Medicine (F.G.), Rheumatology (J.H.W.D.), and Neurology (S.G.M.), and the Hiller Research Center (J.H.W.D.), University Hospital Düsseldorf, the Center for Integrated Oncology, Aachen-Bonn-Cologne-Düsseldorf (G.K., B.-N.B., P.-M.B., N.L., A.R., M. Seifert, C.S., U.G., R.-P.C., K.N., P.J., T.U., S.D.), and the Department of Diagnostic and Interventional Radiology, University Düsseldorf (G.A.), Düsseldorf, Medical Department II, Hematology and Oncology (M.B., H.T.), and the Department of Pathology (I.I.), University Medical Center Schleswig-Holstein, Kiel, the Department of Hematology, Oncology and Cancer Immunology, Campus Virchow, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin (L.W., F.D.), Berlin Institute of Health, Charité Universitätsmedizin Berlin (S.Y., S.H.), and Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (S.Y., S.H.), Berlin, the Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases Heidelberg (N.P.), the Innovation and Service Unit for Bioinformatics and Precision Medicine (D.H.), German Cancer Research Center, the European Molecular Biology Laboratory, Molecular Medicine Partnership Unit (D.F.), German Cancer Consortium (D.H., S.H., F.D.), the Pattern Recognition and Digital Medicine Group, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (D.H.), the Medical Faculty of Heidelberg (J.L.) and the Department of Medicine V (S.D.), Heidelberg University, German Cancer Consortium, partner site Berlin, and German Cancer Research Center (S.H., F.D.), Heidelberg, the Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen (R.K.), and the Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen (M.J.) - all in Germany; and Biomedical Research, Novartis (S.L., P.U.), and Novartis Pharma (H.D.M., H.J.M., J.G.) - both in Basel, Switzerland.
一种罕见的CD4-CD8-仿真抗原受体 (CAR) +外围T细胞淋巴瘤 (PTCL) 在治疗后发展. 遗传分析显示,克隆性血液形成有助于这种致命的淋巴瘤发展.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 免疫治疗是一种免疫疗法.
背景情况:
- 化学抗原受体 (CAR) T细胞疗法是治疗血液恶性瘤的强大工具.
- 复发的初级中枢神经系统淋巴瘤带来了重大的治疗挑战.
研究的目的:
- 为了调查致命的CD4-CD8-CAR+外围T细胞淋巴瘤 (PTCL) 的病因,该淋巴瘤是在CART细胞治疗后发展的.
- 在这种情况下,确定克隆性血液形成在淋巴发育中的作用.
主要方法:
- 一个用tisagenlecleucel治疗的患者的案例研究分析.
- 在淋巴瘤中检测克隆T细胞受体重组的检测,阿菲雷斯产物和自移植.
- 在不同样本中对CD34+干细胞和后代进行体质突变分析 (DNMT3A,TET2).
主要成果:
- 在 tisagenlecleucel 治疗后一个月出现了一种致命的,克隆性CD4-CD8-CAR+ PTCL.
- 克隆T细胞受体重组存在于CAR T细胞制造产品和自身移植中.
- 实体DNMT3A和TET2突变在PTCL,非样本和自身移植中被发现.
- 另外一个TET2突变,在CAR T细胞产品中存在于低频率,表明了克隆性血液形成的贡献.
结论:
- 通过特定的体质突变证明的克隆性血液形成,可以在CAR T细胞治疗后促进淋巴发育.
- 这一案例突出了CAR T细胞治疗的罕见但严重的潜在并发症.
- 需要进一步的研究,以了解和减轻与CAR T细胞治疗和潜在的克隆性血液形成相关的风险.
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