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A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing., Competing Interests: Declaration of interests B.J.S., G.J.O., S.G., V.K., T.F., D.H., A.G., Y.H., A.N., J.C., A.B., S.P., M.A.B., T.P., H.D.E., S.G.G., D.C., A.M., M.L., and R.G.A. were employees of Allogene Therapeutics, Inc. at the time of this work. M.H. reports research support/funding from Takeda Pharmaceutical Company, ADC Therapeutics, Spectrum Pharmaceuticals, and Astellas Pharma; consultancy in the last 2 years with Incyte Corporation, MorphoSys, Kite, Genmab, SeaGen, Gamida Cell, Novartis, Legend Biotech, Kadmon, ADC Therapeutics, Omeros, and Abbvie; speaker’s bureau funding from Sanofi Genzyme, AstraZeneca, BeiGene, and ADC Therapeutics; and has participated in a data monitoring committee for Genetech and Myeloid Therapeutics, Inc. N.N.S. reports consultancy with Miltenyi Biotec; honoraria and speakers bureau funding from Incyte; serving on advisory boards for Kite, BMS, TG therapeutics, Lilly Oncology, Legend, Novartis, Umoja, and Incyte; and receiving institutional research support for clinical trials from Miltenyi Biotec. He is a member of the scientific advisory board for Tundra Therapeutics., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)