Aggressive lymphoma after CD19 CAR T-cell therapy

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Item Type:	Article
Title:	Aggressive lymphoma after CD19 CAR T-cell therapy
Creators Name:	Kobbe, G., Brüggemann, M., Baermann, B.N., Wiegand, L., Trautmann, H., Yousefian, S., Libertini, S., Menssen, H.D., Maier, H.J., Ulrich, P., Gao, J., Bruch, P.M., Liebers, N., Radujkovic, A., Seifert, M., Schniederjohann, C., Paramasivam, N., Fitzgerald, D., Seidel, M., Esposito, I., Germing, U., Cadeddu, R.P., Nachtkamp, K., Jäger, P., Ulrych, T., Fischer, J.C., Rox, J.M., Giesel, F., Koch, R., Antoch, G., Distler, J.H.W., Meuth, S.G., Jacobsen, M., Hübschmann, D., Lu, J., Iaccarino, I., Haas, S., Damm, F. and Dietrich, S.
Abstract:	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.
Keywords:	Bone Marrow Transplantation, Brain Tumor, Cancer, Immunity, Leukemia/Lymphoma, Neurology/Neurosurgery General, Shock, Treatments in Oncology
Source:	New England Journal of Medicine
ISSN:	0028-4793
Publisher:	Massachusetts Medical Society
Volume:	391
Number:	13
Page Range:	1217-1226
Number of Pages:	10
Date:	3 October 2024
Official Publication:	https://doi.org/10.1056/NEJMoa2402730

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