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Aggressive lymphoma after CD19 CAR T-cell therapy: brief report

The development of a fatal, clonal, autonomously proliferating CD4−CD8− chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell rece...

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Main Authors: Kobbe, Guido (Author) , Brüggemann, Monika (Author) , Baermann, Ben-Niklas (Author) , Wiegand, Laura (Author) , Trautmann, Heiko (Author) , Yousefian, Schayan (Author) , Libertini, Silvana (Author) , Menssen, Hans D. (Author) , Maier, Harald J. (Author) , Ulrich, Peter (Author) , Gao, Jingbo (Author) , Bruch, Peter-Martin (Author) , Liebers, Nora (Author) , Radujković, Aleksandar (Author) , Seifert, Marc (Author) , Schniederjohann, Christina (Author) , Paramasivam, Nagarajan (Author) , Fitzgerald, Donnacha (Author) , Seidel, Maximilian (Author) , Esposito, Irene (Author) , Germing, Ulrich (Author) , Cadeddu, Ron-Patrick (Author) , Nachtkamp, Kathrin (Author) , Jäger, Paul (Author) , Ulrych, Thomas (Author) , Fischer, Johannes C. (Author) , Rox, Jutta M. (Author) , Giesel, Frederik L. (Author) , Koch, Raphael (Author) , Antoch, Gerald (Author) , Distler, Jörg H. W. (Author) , Meuth, Sven G. (Author) , Jacobsen, Malte (Author) , Hübschmann, Daniel (Author) , Lu, Junyan (Author) , Iaccarino, Ingram (Author) , Haas, Simon (Author) , Damm, Frederik (Author) , Dietrich, Sascha (Author)
Format: Article (Journal)
Language:English
Published: October 2, 2024
In: The New England journal of medicine
Year: 2024, Volume: 391, Issue: 13, Pages: 1217-1226
ISSN:1533-4406
DOI:10.1056/NEJMoa2402730
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1056/NEJMoa2402730
Verlag, lizenzpflichtig, Volltext: https://www.nejm.org/doi/full/10.1056/NEJMoa2402730
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Author Notes:G. Kobbe, M. Brüggemann, B.-N. Baermann, L. Wiegand, H. Trautmann, S. Yousefian, S. Libertini, H.D. Menssen, H.J. Maier, P. Ulrich, J. Gao, P.-M. Bruch, N. Liebers, A. Radujkovic, M. Seifert, C. Schniederjohann, N. Paramasivam, D. Fitzgerald, M. Seidel, I. Esposito, U. Germing, R.-P. Cadeddu, K. Nachtkamp, P. Jäger, T. Ulrych, J.C. Fischer, J.M. Rox, F. Giesel, R. Koch, G. Antoch, J.H.W. Distler, S.G. Meuth, M. Jacobsen, D. Hübschmann, J. Lu, I. Iaccarino, S. Haas, F. Damm, and S. Dietrich

MARC

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520 |a The development of a fatal, clonal, autonomously proliferating CD4−CD8− chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic DNMT3A and TET2 mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant. The PTCL harbored an additional somatic TET2 mutation, which was already detectable in the CAR T-cell apheresis product and the final CAR T-cell product at very low frequencies, providing evidence that clonal hematopoiesis had contributed to lymphomagenesis. Shortly after a patient received CAR T-cell therapy for relapsed CNS lymphoma, an aggressive CAR+ T-cell lymphoma was diagnosed. Subsequent analysis revealed the presence of an abnormal clone in an early apheresis specimen. 
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