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Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa

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Abstract

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.

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Authors and Affiliations

  1. Service de Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker-Pasteur, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France

    Romain Guery, Fanny Lanternier, Marc Lecuit, Olivier Lortholary & Claire Aguilar

  2. Service d’Hématologie Adultes, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France

    Felipe Suarez, David Sibon, Laurent Frenzel, Olivier Hermine & Ambroise Marçais

  3. Laboratoire de Microbiologie Clinique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France

    Marie Elisabeth Bougnoux, Hervé Lecuyer & Véronique Avettand-Fenoel

  4. Service de Réanimation, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France

    Jean-Herlé Raphalen

  5. Département de Radiothérapie-Oncologie-Hématologie, Centre Hospitalier Universitaire de La Guadeloupe, Pointe à Pitre, France

    Philippe Helias

  6. Service d’Oncologie-Hématologie, Centre Hospitalier Universitaire de La Martinique, Hôpital Pierre Zobda Quitman, Fort de France, France

    Philippe Renaudier

  7. Centre Hospitalier de Cayenne, Guyane Française, France

    Florin Santa

  8. Biology of Infection Unit, Institut Pasteur, Inserm U1117, Paris, France

    Marc Lecuit

  9. Laboratoire d’Onco-Hématologie, Institut Necker-Enfants Malades, INSERM U1151, Université de Paris, Paris, France

    Ambroise Marçais

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  1. Romain Guery
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Contributions

R.G., O.L., O.H., C.A., and A.M. designed the research. R.G. collected the data. R.G., C.A., and A.M. analyzed results and made the figures. R.G., C.A., and A.M. wrote the paper. R.G., F.S., F.L., D.S., L.F., J.H., P.H., P.R., F.S., M.L., O.L., O.H., C.A, and A.M. took care of patients. O.L., O.H., F.S., F.L., M.B., H.L., V.A., D.S., L.F., J.H., P.H., P.R., F.S., and M.L. reviewed and contributed to the writing of the manuscript.

Ethical approval and consent to participate.

This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was obtained from the CPP Ile de France Ethical Board (CNIL: Number 1692254, Registration Number 000001072) and all surviving patients gave written informed consent.

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Correspondence to Ambroise Marçais.

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Guery, R., Suarez, F., Lanternier, F. et al. Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa. Ann Hematol 100, 2813–2824 (2021). https://doi.org/10.1007/s00277-021-04622-9

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