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Acute myeloid leukemia after CAR T-cell therapy: role of pre-existing clonal hematopoiesis and inflammation in leukemogenesis

Bone Marrow Transplantation (2025)Cite this article

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Among the late complications associated with CAR T-cell therapies, secondary malignancies, and particularly acute myeloid leukemia, are a growing concern. Here, we report four cases of acute myeloid leukemia (AML) that emerged following anti-CD19 CAR T-cell therapy. We assess clonal evolution and factors contributing to leukemogenesis.

A 56-year-old male received axi-cel for Stage IV intestinal for diffuse large B-cell lymphoma (DLBCL), which was refractory to two prior lines of therapy. At the time of lymphodepletion conditioning, clinical examination showed mild alteration of general state with Karnofski score of 70% and recent loss of 6 Kg weight. Complete blood count (CBC) was normal (Table 1). Following leukapheresis, bridging therapy with ifosfamide and etoposide was administered; however, the disease progressed before lymphodepleting conditioning. The patient developed grade 2 CRS by day 4, requiring two doses of tocilizumab and dexamethasone from days 6 to 9. On day 8, he experienced septic shock due to intestinal perforation, confirmed as secondary to tumor necrosis upon pathological examination after intestinal resection. A neuroendocrine tumor was also identified in the appendix but was not implicated in the perforation.

Table 1 Primary and secondary disease characteristics and treatment modalities.
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All data generated or analysed during this study are included in this published article or in its supplementary information files.

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Acknowledgements

We sincerely thank the Capucine Association for their continuous support of our research.

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Authors and Affiliations

  1. CHU de Lille, Maladies du Sang, Université de Lille, 59000, Lille, France

    Paul Chauvet, Cynthia Saade, David Beauvais, Micha Srour, Leonardo Magro, Valérie Coiteux, Nicolas Gazeau & Ibrahim Yakoub-Agha

  2. Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France

    Paul Chauvet & Suman Mitra

  3. CHU de Lille, Institut d’Immunologie, Centre de Biologie Pathologie, Université de Lille, 59000, Lille, France

    Julie Demaret

  4. CHU de Nîmes, Hématologie Clinique, Nîmes, France

    Nicolas Branche

  5. Institute of Medical Genetics, CHU Lille, Avenue Eugène Avinée, 59037 Lille Cedex and France Univ. Lille, Lille, France

    Catherine Roche-Lestienne

  6. Laboratory of Hematology, Lille University Hospital, Lille, France

    Laurène Fenwarth & Elise Fournier

  7. CHU de Caen, Institut d’Hématologie, Université de Caen-Normandie, Caen, France

    Gandhi Damaj

  8. Univ Lille, INSERM U1286, Infinite, 59000, Lille, France

    Ibrahim Yakoub-Agha

Authors
  1. Paul Chauvet
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  2. Cynthia Saade
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Contributions

PC, GD and, IY-A: conceptualized the subject for this work. PC and CS wrote the original draft. PC drown the figures. JD, CRL, EF, LF carried out the cytokine essays, cytogenetics and FISH and NGS respectively. PC, CS, DB, LM, MS, VC, NG, NB, GD and IY-A took care of the patients. All co-authors revised the manuscript and approved the final version.

Corresponding author

Correspondence to Paul Chauvet.

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Competing interests

PC: no conflict of interest related to this study. CS: no conflict of interest related to this study. JD: no conflict of interest related to this study. DB: no conflict of interest related to this study. LM: no conflict of interest related to this study. MS: no conflict of interest related to this study. VC: no conflict of interest related to this study. NG: no conflict of interest related to this study. NB: no conflict of interest related to this study. CRL: no conflict of interest related to this study. LF: no conflict of interest related to this study. EF: no conflict of interest related to this study. GD: no conflict of interest related to this study. IY-A: received honorarium from Gikead/Kite, BMS, Novartis and AstraZeneca.

Ethics approval and consent to participate

All analysis presented here were performed in accordance with the relevant guidelines and regulations. All participants provided written informed consent under ethics committee-approved biobank protocol “CAR-LILLE”(CPP ID-RCB: 2020-A01935-34) in accordance with the Declaration of Helsinki.

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Chauvet, P., Saade, C., Demaret, J. et al. Acute myeloid leukemia after CAR T-cell therapy: role of pre-existing clonal hematopoiesis and inflammation in leukemogenesis. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02700-4

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