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Adenovirus-induced hemorrhagic cystitis after CD19-targeted chimeric antigen receptor T-cell therapy in a patient with large B-cell lymphoma

    Irene Medina‡

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    ‡Authors contributed equally

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    ,
    Cecilia Carpio‡

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Isabel Ruiz-Camps

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Department of Infectious Diseases, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    ,
    Adaia Albasanz-Puig

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Department of Infectious Diseases, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    ,
    Oriana Lopez-Godino

    Department of Hematology, Hospital Universitario Morales Meseguer, 30008, Murcia, Spain

    ,
    Juliana Esperalba

    Department of Microbiology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    ,
    Francisco Beas

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    ,
    Mario Sanchez-Salinas

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    ,
    Gloria Iacoboni

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    &
    Pere Barba

    *Author for correspondence: Tel.: +34 932 746 100;

    E-mail Address: pbarba@vhio.net

    Department of Hematology, Experimental Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, 08035, Barcelona, Spain

    Department of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Published Online:https://doi.org/10.2217/imt-2023-0111

    Chimeric antigen receptor (CAR) T cells targeting CD19 have changed the treatment landscape of patients with relapsed/refractory diffuse large B-cell lymphoma. Infections are one of the most frequent complications after CAR T-cell therapy. Most of these infections are bacterial, although viral infections can also occur in this setting. Adenovirus-induced hemorrhagic cystitis is a rare infectious complication and is usually observed after bone marrow or solid organ transplantation. Herein we report a case of adenovirus-induced hemorrhagic cystitis in a patient experiencing urinary symptoms within the first month after CAR T-cell infusion. Based on our experience and a literature review, we discuss the diagnostic approach and potential treatment options for this infrequent infection after CAR T-cell therapy.

    Plain language summary

    Lymphoma is an aggressive blood cell cancer. A treatment called chimeric antigen receptor (CAR) T-cell therapy has recently been developed for patients with lymphoma and other blood cancers. CAR T-cell therapy is based on the genetic change of the patient's T cells. T cells are a type of white blood cell, which help to attack cancer. CAR T-cell treatment is very effective, but it also carries a risk of adverse events, including infections. These infections can be caused by bacteria or viruses and can affect several organs, including the bladder. Patients with blood cancers who develop bladder infections can have severe pain and bleeding. These bleeding bladder infections are mostly caused by adenovirus or BK virus and are usually seen in patients who have received a bone marrow transplant. However, these infections are rarely observed in patients receiving CAR T cells. We report here a case of bleeding bladder infection caused by adenovirus in a patient receiving CAR T-cell therapy. We discuss the diagnostic approach and possible treatment options for this rare infection in CAR T-cell patients.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Schuster SJ, Bishop MR, Tam CS et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl. J. Med. 380(1), 45–56 (2019).
    • 2. Neelapu SS, Locke FL, Bartlett NL et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 377(26), 2531–2544 (2017).
    • 3. Neelapu SS, Jacobson CA, Ghobadi A et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood 141(19), 2307–2315 (2023). • Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 4. Schuster SJ, Tam CS, Borchmann P et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 22(10), 1403–1415 (2021).
    • 5. Kwon M, Iacoboni G, Reguera JL et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica 108(1), 110–121 (2023).
    • 6. Iacoboni G, Villacampa G, Martinez-Cibrian N et al. Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Cancer Med. 10(10), 3214–3223 (2021).
    • 7. Stewart AG, Henden AS. Infectious complications of CAR T-cell therapy: a clinical update. Ther. Adv. Infect. Dis. 8, 1–11 (2021). • Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 8. Hill JA, Li D, Hay KA et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 131(1), 121–130 (2018). •• Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 9. Los-Arcos I, Iacoboni G, Aguilar-Guisado M et al. Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper. Infection 49(2), 215–231 (2021). •• Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 10. D'Amico MJ, Foss H, Uhr A, Rudnick B, Kloniecke E, Gomella LG. Hemorrhagic cystitis: a review of the literature and treatment options. Can. J. Urol. 29(5), 11276–11283 (2022). •• Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 11. Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin. Microbiol. Rev. 27(3), 441–462 (2014).
    • 12. Lion T. Adenovirus persistence, reactivation, and clinical management. FEBS Lett. 593(24), 3571–3582 (2019).
    • 13. de Padua Silva L, Patah PA, Saliba RM et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica 95(7), 1183–1190 (2010).
    • 14. Khan AM, Ajmal Z, Zahra FT, Ramani A, Zackon I. Hemorrhagic cystitis secondary to adenovirus and BK virus infection in a diffuse large B-cell lymphoma patient with recent CAR T-cell therapy. Case Rep. Hematol. 2020, 1–4 (2020).
    • 15. Dodge MJ, MacNeil KM, Tessier TM, Weinberg JB, Mymryk JS. Emerging antiviral therapeutics for human adenovirus infection: recent developments and novel strategies. Antiviral Res. 188, 1–13 (2021).
    • 16. Rejeski K, Perez A, Sesques P et al. CAR-HEMATOTOX: a model for CAR T-cell–related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood 138(24), 2499–2513 (2021).
    • 17. Bachy E, Le Gouill S, Di Blasi R et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat. Med. 28(10), 2145–2154 (2022).
    • 18. Márquez-Algaba E, Iacoboni G, Pernas B et al. Impact of cytomegalovirus replication in patients with aggressive B cell lymphoma treated with chimeric antigen receptor T cell therapy. Transplant. Cell. Ther. 28(12), 851.e1–851.e8 (2022).
    • 19. Chen G, Herr M, Nowak J et al. Cytomegalovirus reactivation after CD19 CAR T-cell therapy is clinically significant. Haematologica 108(2), 615–620 (2023).
    • 20. Spanjaart AM, van der Valk FM, van Rooijen G, Brouwer MC, Kersten MJ. Confused about confusion. N. Engl. J. Med. 386(1), 80–87 (2022).
    • 21. Matthes-Martin S, Feuchtinger T, Shaw PJ et al. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). Transpl. Infect. Dis. 14(6), 555–563 (2012). • Useful to understand CAR T-cell therapy, infections after treatment, hemorrhagic cystitis and adenoviral infections.
    • 22. Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood 116(25), 5476–5485 (2010).
    • 23. Faraci M, Cuzzubbo D, Lanino E et al. Low dosage cidofovir without probenecid as treatment for BK virus hamorrhagic cystitis after hemopoietic stem cell transplant. Pediatr. Infect. Dis. J. 28(1), 55–57 (2009).