{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:42:02Z","timestamp":1793108522172,"version":"4.5.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Clonal hematopoiesis of indeterminate potential (CHIP) has been well-characterized in patients receiving chemotherapy and hematopoietic cell transplantation. However, its immunologic relevance and potential role in modulating chimeric antigen receptor T-cell (CAR-T) therapy-related toxicities, inflammation, and clinical outcomes remains incompletely defined. In this exploratory study of 104 CAR-T recipients, we investigated the prognostic impact of pre-existing CHIP clones on toxicity and survival, and examined CHIP-associated inflammatory proteomic signatures leveraging longitudinal serum samples. Overall CHIP status was not associated with inflammatory toxicities, outcomes, or systemic inflammatory profiles. Analysis of clonal dynamics revealed\n                    <jats:italic>TP53-<\/jats:italic>\n                    and\n                    <jats:italic>ASXL1<\/jats:italic>\n                    -mutated clones to be the dominant expanding CHIP clones post-infusion, whereas\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    - and\n                    <jats:italic>PPM1D<\/jats:italic>\n                    -mutated clones showed reduced clonal abundance over time. Notably,\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutated CHIP was linked to lower platelet and hemoglobin levels, a higher baseline CAR-HEMATOTOX score, inferior clinical outcomes, and a distinct inflammatory signature. These findings identify\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutated CHIP in CAR-T-treated patients as a high-risk CHIP genotype compared with other CHIP mutations. Importantly, patients who developed treatment-emergent myeloid neoplasms after CAR T-cell therapy exhibited distinct patterns of clonal expansion and inflammatory profiles. Together, these findings support a risk-adapted approach prioritizing longitudinal monitoring of\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutated CHIP, especially in patients with high CAR-HEMATOTOX scores who develop cytopenias.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03083-1","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:57:07Z","timestamp":1787554627000},"page":"2540-2551","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1050-0258","authenticated-orcid":false,"given":"Giulia","family":"Rappa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ziemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieron","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linus","family":"Kruk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3837-8055","authenticated-orcid":false,"given":"Samar","family":"Shamas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6900-7212","authenticated-orcid":false,"given":"Amelie","family":"Muth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayleen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-6490","authenticated-orcid":false,"given":"Cristina","family":"Zucchinetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2900-5351","authenticated-orcid":false,"given":"Savanna","family":"S\u00fc\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Rothenberg-Thurley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Holzem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Tix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Petrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianka","family":"Ksienzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Bentenrieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6276-8002","authenticated-orcid":false,"given":"Katharina S.","family":"G\u00f6tze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-5839","authenticated-orcid":false,"given":"Fabian","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-7280","authenticated-orcid":false,"given":"Veit","family":"B\u00fccklein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-0251","authenticated-orcid":false,"given":"Kai","family":"Rejeski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9154-9469","authenticated-orcid":false,"given":"Marion","family":"Subklewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"3083_CR1","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1038\/s41409-025-02691-2","volume":"60","author":"Y Dong","year":"2025","unstructured":"Dong Y, Yang T, Zhao M, Song F, Chen R, Zhang M, et al. Safety and efficacy of autologous humanized CD19 CAR-T cell therapy for relapsed\/refractory B-cell non-Hodgkin lymphoma. Bone Marrow Transpl. 2025;60:1445\u201350.","journal-title":"Bone Marrow Transpl"},{"key":"3083_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1470-2045(21)00591-X","volume":"23","author":"CA Jacobson","year":"2022","unstructured":"Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23:91\u2013103.","journal-title":"Lancet Oncol"},{"key":"3083_CR3","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1056\/NEJMoa1914347","volume":"382","author":"M Wang","year":"2020","unstructured":"Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory Mantle-cell lymphoma. N Engl J Med. 2020;382:1331\u201342.","journal-title":"N Engl J Med"},{"key":"3083_CR4","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1056\/NEJMoa2213614","volume":"388","author":"P Rodriguez-Otero","year":"2023","unstructured":"Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388:1002\u201314.","journal-title":"N Engl J Med"},{"key":"3083_CR5","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1038\/s41591-025-03813-5","volume":"31","author":"K Rejeski","year":"2025","unstructured":"Rejeski K, Hill JA, Dahiya S, Jain MD. Noncanonical and mortality-defining toxicities of CAR T cell therapy. Nat Med. 2025;31:2132\u201346.","journal-title":"Nat Med"},{"key":"3083_CR6","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1038\/s41591-024-03084-6","volume":"30","author":"DM Cordas Dos Santos","year":"2024","unstructured":"Cordas Dos Santos DM, Tix T, Shouval R, Gafter-Gvili A, Alberge JB, Cliff ERS, et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nat Med. 2024;30:2667\u201378.","journal-title":"Nat Med"},{"key":"3083_CR7","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.3390\/cells12212581","volume":"12","author":"A Dibas","year":"2023","unstructured":"Dibas A, Rhiel M, Patel VB, Andrieux G, Boerries M, Cornu TI, et al. Cell-based models of \u2018Cytokine Release Syndrome\u2019 endorse CD40L and granulocyte\u2013macrophage colony-stimulating factor knockout in chimeric antigen receptor T cells as mitigation strategy. Cells. 2023;12:2581.","journal-title":"Cells"},{"key":"3083_CR8","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","volume":"36","author":"JD Khoury","year":"2022","unstructured":"Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms. Leukemia. 2022;36:1703\u201319.","journal-title":"Leukemia"},{"key":"3083_CR9","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1182\/bloodadvances.2021005747","volume":"6","author":"R Teipel","year":"2022","unstructured":"Teipel R, Kroschinsky F, Kramer M, Kretschmann T, Egger-Heidrich K, Kr\u00fcger T, et al. Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment. Blood Adv. 2022;6:1941\u20136.","journal-title":"Blood Adv"},{"key":"3083_CR10","doi-asserted-by":"crossref","unstructured":"Gibson CJ, Lindsley RC, Tchekmedyian V, Mar BG, Shi J, Jaiswal S, et al. Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma. J Clin Oncol. 2017;35:1598\u2013605.","DOI":"10.1200\/JCO.2016.71.6712"},{"key":"3083_CR11","doi-asserted-by":"publisher","first-page":"4333","DOI":"10.1158\/1078-0432.CCR-25-1587","volume":"31","author":"ZM Avigan","year":"2025","unstructured":"Avigan ZM, Catlett J, Bodnar S, Pan D, Aleman A, Sheng T, et al. Clonal hematopoiesis and inflammation predict hematologic toxicity and secondary myeloid malignancies after B-cell maturation antigen\u2013directed chimeric antigen receptor T-cell therapy. Clin Cancer Res. 2025;31:4333\u201344.","journal-title":"Clin Cancer Res"},{"key":"3083_CR12","doi-asserted-by":"publisher","first-page":"e957","DOI":"10.1097\/HS9.0000000000000957","volume":"7","author":"V Panagiota","year":"2023","unstructured":"Panagiota V, Kerschbaum JF, Penack O, Stein CM, Arends CM, Koenecke C, et al. Clinical implications and dynamics of clonal hematopoiesis in anti-CD19 CAR T-cell treated patients. HemaSphere. 2023;7:e957.","journal-title":"HemaSphere"},{"key":"3083_CR13","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1038\/s41375-025-02605-7","volume":"39","author":"N Gazeau","year":"2025","unstructured":"Gazeau N, Beauvais D, Tilmont R, Srour M, Ferrant E, Safar V, et al. Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time? Leukemia. 2025;39:1714\u201322.","journal-title":"Leukemia"},{"key":"3083_CR14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/ajh.27655","volume":"100","author":"MV Shah","year":"2025","unstructured":"Shah MV, Arber DA, Hiwase DK. TP53-mutated myeloid neoplasms: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2025;100:88\u2013115.","journal-title":"Am J Hematol"},{"key":"3083_CR15","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1182\/bloodadvances.2025015981","volume":"9","author":"JN Gustine","year":"2025","unstructured":"Gustine JN, Branagan AR, Cirstea DD, Rexha F, Han R, Yee AJ, et al. Impact of clonal hematopoiesis on clinical outcomes to BCMA CAR-T in multiple myeloma. Blood Adv. 2025;9:3026\u201330.","journal-title":"Blood Adv"},{"key":"3083_CR16","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1182\/bloodadvances.2021004554","volume":"5","author":"PG Miller","year":"2021","unstructured":"Miller PG, Sperling AS, Brea EJ, Leick MB, Fell GG, Jan M, et al. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. Blood Adv. 2021;5:2982\u20136.","journal-title":"Blood Adv"},{"key":"3083_CR17","first-page":"927.e1","volume":"30","author":"SR Goldsmith","year":"2024","unstructured":"Goldsmith SR, Shouse G, Wong FL, Bosworth A, Iukuridze A, Chen S, et al. Clonal hematopoiesis is associated with severe cytokine release syndrome in patients treated with chimeric antigen receptor T-cell (CART) therapy. Transpl Cell Ther. 2024;30:927.e1\u2013927.e9.","journal-title":"Transpl Cell Ther"},{"key":"3083_CR18","first-page":"S236","volume":"31","author":"SG Carlson","year":"2025","unstructured":"Carlson SG, Puliafito B, Brown P, Kawai K, Senaratne TN, Lee TD, et al. Impact of clonal hematopoiesis of indeterminate potential (CHIP) on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy. Transpl Cell Ther. 2025;31:S236.","journal-title":"Transpl Cell Ther"},{"key":"3083_CR19","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1158\/2643-3230.BCD-21-0177","volume":"3","author":"NY Saini","year":"2022","unstructured":"Saini NY, Swoboda DM, Greenbaum U, Ma J, Patel RD, Devashish K, et al. Clonal hematopoiesis is associated with increased risk of severe neurotoxicity in axicabtagene ciloleucel therapy of large B-cell lymphoma. Blood Cancer Discov. 2022;3:385\u201393. Sep 6.","journal-title":"Blood Cancer Discov"},{"key":"3083_CR20","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","volume":"25","author":"DW Lee","year":"2019","unstructured":"Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transpl. 2019;25:625\u201338.","journal-title":"Biol Blood Marrow Transpl"},{"key":"3083_CR21","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1182\/bloodadvances.2023011767","volume":"8","author":"K Rejeski","year":"2024","unstructured":"Rejeski K, Wang Y, Hansen DK, Iacoboni G, Bachy E, Bansal R, et al. Applying the EHA\/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality. Blood Adv. 2024;8:1857\u201368.","journal-title":"Blood Adv"},{"key":"3083_CR22","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1038\/s41409-024-02278-3","volume":"59","author":"EC Liang","year":"2024","unstructured":"Liang EC, Rejeski K, Fei T, Albittar A, Huang JJ, Portuguese AJ, et al. Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity. Bone Marrow Transpl. 2024;59:910\u20137.","journal-title":"Bone Marrow Transpl"},{"key":"3083_CR23","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1038\/s41375-018-0034-z","volume":"32","author":"M Rothenberg-Thurley","year":"2018","unstructured":"Rothenberg-Thurley M, Amler S, Goerlich D, K\u00f6hnke T, Konstandin NP, Schneider S, et al. Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia. Leukemia. 2018;32:1598\u2013608.","journal-title":"Leukemia"},{"key":"3083_CR24","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1182\/blood-2025-930","volume":"146","author":"Z Xie","year":"2025","unstructured":"Xie Z, Castaneda Puglianini OA, Nishihori T, Grajales-Cruz A, Cheng P, Blue B, et al. Beyond chip: Ccrs predicts prolonged cytopenias and inferior survival following anti-BCMA CAR-T in multiple myeloma. Blood. 2025;146:930\u2013930.","journal-title":"Blood"},{"key":"3083_CR25","doi-asserted-by":"publisher","first-page":"eadu9790","DOI":"10.1126\/scitranslmed.adu9790","volume":"17","author":"MB Khelil","year":"2025","unstructured":"Khelil MB, Arbab A, Srikanthan J, Kovandzic LM, Verg\u00e9 V, Pag\u00e8s A, et al. CAR T cell\u2013mediated bone marrow inflammation causes hematotoxicity and favors clonal hematopoiesis. Sci Transl Med. 2025;17:eadu9790.","journal-title":"Sci Transl Med"},{"key":"3083_CR26","doi-asserted-by":"publisher","first-page":"eadg3919","DOI":"10.1126\/sciadv.adg3919","volume":"9","author":"K Rejeski","year":"2023","unstructured":"Rejeski K, Perez A, Iacoboni G, Blumenberg V, B\u00fccklein VL, V\u00f6lkl S, et al. Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion. Sci Adv. 2023;9:eadg3919.","journal-title":"Sci Adv"},{"key":"3083_CR27","doi-asserted-by":"publisher","first-page":"eaan4673","DOI":"10.1126\/science.aan4673","volume":"366","author":"S Jaiswal","year":"2019","unstructured":"Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science. 2019;366:eaan4673.","journal-title":"Science"},{"key":"3083_CR28","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.stem.2017.07.010","volume":"21","author":"CC Coombs","year":"2017","unstructured":"Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, Jonsson P, et al. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. Cell Stem Cell. 2017;21:374\u2013382.e4.","journal-title":"Cell Stem Cell"},{"key":"3083_CR29","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1038\/s41588-020-00710-0","volume":"52","author":"KL Bolton","year":"2020","unstructured":"Bolton KL, Ptashkin RN, Gao T, Braunstein L, Devlin SM, Kelly D, et al. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat Genet. 2020;52:1219\u201326.","journal-title":"Nat Genet"},{"key":"3083_CR30","doi-asserted-by":"publisher","first-page":"e184285","DOI":"10.1172\/JCI184285","volume":"136","author":"S Chen","year":"2026","unstructured":"Chen S, Barajas S, Vemula S, Yang Y, Simpson E, Gao H, et al. Mutant p53 promotes clonal hematopoiesis by generating a chronic inflammatory microenvironment. J Clin Invest. 2026;136:e184285.","journal-title":"J Clin Invest"},{"key":"3083_CR31","doi-asserted-by":"publisher","first-page":"4690","DOI":"10.1158\/1078-0432.CCR-24-1798","volume":"30","author":"T Tix","year":"2024","unstructured":"Tix T, Alhomoud M, Shouval R, Cliff ERS, Perales MA, Cordas Dos Santos DM, et al. Second primary malignancies after CAR T-cell therapy: a systematic review and meta-analysis of 5,517 lymphoma and myeloma patients. Clin Cancer Res. 2024;30:4690\u2013700.","journal-title":"Clin Cancer Res"},{"key":"3083_CR32","first-page":"990","volume":"30","author":"R Lorenc","year":"2024","unstructured":"Lorenc R, Shouval R, Flynn JR, Devlin SM, Saldia A, De Abia AL, et al. Subsequent malignancies after CD19-targeted chimeric antigen receptor T cells in patients with lymphoma. Transpl Cell Ther. 2024;30:990\u20131000.","journal-title":"Transpl Cell Ther"},{"key":"3083_CR33","doi-asserted-by":"publisher","first-page":"5215","DOI":"10.1182\/bloodadvances.2024012929","volume":"8","author":"KT Nead","year":"2024","unstructured":"Nead KT, Kim T, Joo L, McDowell TL, Wong JW, Chan ICC, et al. Impact of cancer therapy on clonal hematopoiesis mutations and subsequent clinical outcomes. Blood Adv. 2024;8:5215\u201324.","journal-title":"Blood Adv"},{"key":"3083_CR34","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1182\/blood.2020007445","volume":"137","author":"MD Jain","year":"2021","unstructured":"Jain MD, Zhao H, Wang X, Atkins R, Menges M, Reid K, et al. Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma. Blood. 2021;137:2621\u201333.","journal-title":"Blood"},{"key":"3083_CR35","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1158\/2643-3230.BCD-23-0056","volume":"5","author":"RG Faramand","year":"2024","unstructured":"Faramand RG, Lee SB, Jain MD, Cao B, Wang X, Rejeski K, et al. Baseline serum inflammatory proteins predict poor CAR T outcomes in diffuse large B-cell lymphoma. Blood Cancer Discov. 2024;5:106\u201313.","journal-title":"Blood Cancer Discov"},{"key":"3083_CR36","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1182\/blood.2020010543","volume":"138","author":"K Rejeski","year":"2021","unstructured":"Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, et al. CAR-HEMATOTOX: a model for CAR T-cell\u2013related hematologic toxicity in relapsed\/refractory large B-cell lymphoma. Blood. 2021;138:2499\u2013513.","journal-title":"Blood"},{"key":"3083_CR37","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1182\/blood.2024024104","volume":"144","author":"MJ Frigault","year":"2024","unstructured":"Frigault MJ, Graham CE, Berger TR, Ritchey J, Horick NK, El-Jawahri A, et al. Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies. Blood. 2024;144:1153\u201367.","journal-title":"Blood"},{"key":"3083_CR38","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41584-023-01053-w","volume":"20","author":"E Landy","year":"2024","unstructured":"Landy E, Carol H, Ring A, Canna S. Biological and clinical roles of IL-18 in inflammatory diseases. Nat Rev Rheumatol. 2024;20:33\u201347.","journal-title":"Nat Rev Rheumatol"},{"key":"3083_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96256-0","volume":"11","author":"D Ruggiero","year":"2021","unstructured":"Ruggiero D, Nutile T, Nappo S, Tirozzi A, Bellenguez C, Leutenegger AL, et al. Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity. Sci Rep. 2021;11:16821.","journal-title":"Sci Rep"},{"key":"3083_CR40","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.ccr.2011.05.007","volume":"19","author":"T Schmidt","year":"2011","unstructured":"Schmidt T, Masouleh BK, Loges S, Cauwenberghs S, Fraisl P, Maes C, et al. Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1+ leukemia. Cancer Cell. 2011;19:740\u201353.","journal-title":"Cancer Cell"},{"key":"3083_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21099-2","volume":"12","author":"R Yang","year":"2021","unstructured":"Yang R, Sun L, Li CF, Wang YH, Yao J, Li H, et al. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat Commun. 2021;12:832.","journal-title":"Nat Commun"},{"key":"3083_CR42","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.1038\/s41375-025-02766-5","volume":"39","author":"J Frede","year":"2025","unstructured":"Frede J, Poller JC, Shi K, Stuart H, Sotudeh N, Havig C, et al. The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma. Leukemia. 2025;39:3004\u201314.","journal-title":"Leukemia"},{"key":"3083_CR43","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1182\/bloodadvances.2019001157","volume":"4","author":"JF Soerensen","year":"2020","unstructured":"Soerensen JF, Aggerholm A, Kerndrup GB, Hansen MC, Ewald IKL, Bill M, et al. Clonal hematopoiesis predicts development of therapy-related myeloid neoplasms post\u2013autologous stem cell transplantation. Blood Adv. 2020;4:885\u201392.","journal-title":"Blood Adv"},{"key":"3083_CR44","doi-asserted-by":"crossref","unstructured":"Waldschmidt J, Fandrei D, Hecker JS, Meggendorfer M, Truger M, Reinhard F, et al. Flare of clonal hematopoiesis, TP53 expansion and prior melphalan drive post-CAR-T myeloid disorders in multiple myeloma. Leukemia. 2026;40:1054\u20137.","DOI":"10.1038\/s41375-026-02941-2"},{"key":"3083_CR45","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1001\/jamaoncol.2024.5412","volume":"11","author":"SA Patel","year":"2025","unstructured":"Patel SA, Spiegel JY, Dahiya S. Second primary cancer after chimeric antigen receptor\u2013T-cell therapy: a review. JAMA Oncol. 2025;11:174.","journal-title":"JAMA Oncol"},{"key":"3083_CR46","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s12276-023-01136-4","volume":"56","author":"R Singh","year":"2024","unstructured":"Singh R, Kim YH, Lee SJ, Eom HS, Choi BK. 4-1BB immunotherapy: advances and hurdles. Exp Mol Med. 2024;56:32\u20139.","journal-title":"Exp Mol Med"},{"key":"3083_CR47","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1615\/CritRevImmunol.v29.i3.10","volume":"29","author":"WL Redmond","year":"2009","unstructured":"Redmond WL, Ruby CE, Weinberg AD. The role of OX40-mediated co-stimulation in T-cell activation and survival. Crit Rev Immunol. 2009;29:187\u2013201.","journal-title":"Crit Rev Immunol"},{"key":"3083_CR48","doi-asserted-by":"publisher","first-page":"e1438800","DOI":"10.1080\/2162402X.2018.1438800","volume":"7","author":"K Jung","year":"2018","unstructured":"Jung K, Ha JH, Kim JE, Kim JA, Kim YJ, Kim CH, et al. Heterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8+ T cells. OncoImmunology. 2018;7:e1438800.","journal-title":"OncoImmunology"},{"key":"3083_CR49","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1016\/j.ymthe.2023.06.015","volume":"31","author":"N Zhang","year":"2023","unstructured":"Zhang N, Liu X, Qin J, Sun Y, Xiong H, Lin B, et al. LIGHT\/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment. Mol Ther. 2023;31:2575\u201390.","journal-title":"Mol Ther"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03083-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03083-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03083-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:58:46Z","timestamp":1793105926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03083-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":49,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["3083"],"URL":"https:\/\/doi.org\/10.1038\/s41375-026-03083-1","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"assertion":[{"value":"18 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"TT Kite\/Gilead: Travel support. VB Abbvie: Honoraria, Tavel support; AMGEN: Honoraria, Consultancy, Travel support; BMS: Research funding; Kite\/Gilead: Research funding, Consultancy, Travel support; Miltenyi Biotech: Research support; Johnson&Johnson: Research support, Consultancy, Travel support; Pierre Fabr\u00e9: Consultancy, Travel Support; Pfizer: Honoraria; Priothera: Consultancy; Roche: Honoraria; Takeda: Research support. KR Kite\/Gilead: Research Funding, Consultancy, Honoraria and travel support; Novartis: Honoraria; BMS\/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support. CSL Behring: Consultancy. MSD: Honoraria. Grifols: Honoraria. MS receives industry research support from Amgen, Roche, Seattle Genetics, and serves as a consultant\/advisor to AbbVie, Gilead\/Kite, Interius, Johnson & Johnson, Molecular Partners, Novartis, Otsuka. She serves on the speakers\u2019 bureau at Amgen, Bristol Myers Squibb\/Celgene, Gilead\/Kite, Miltenyi Biotec, Novartis, Roche, and Takeda. All remaining authors declare no competing financial interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors confirm that all methods were performed in accordance with the relevant guidelines and regulations. All human samples were collected with written informed consent in accordance with the Declaration of Helsinki and approval by the Institutional Review Board of the LMU Munich.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Portions of this manuscript were edited for clarity and conciseness using OpenAI\u2019s ChatGPT. The AI-assisted modifications were restricted to improving readability and conciseness, with all scientific content and conclusions remaining the sole responsibility of the authors.","order":3,"name":"Ethics","label":"Declaration of AI-assisted technologies in the writing process","group":{"name":"EthicsHeading","label":"Ethics"}}]}}