{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:33Z","timestamp":1760145753795,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2014Ricerca Corrente Annual Program 2025"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells\/\u00b5L), his c-reactive protein was 27 mg\/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg\/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute\/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.<\/jats:p>","DOI":"10.3390\/jof10080584","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T06:41:31Z","timestamp":1724049691000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab"],"prefix":"10.3390","volume":"10","author":[{"given":"Paolo","family":"Pavone","sequence":"first","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5228-7258","authenticated-orcid":false,"given":"Laura","family":"Arletti","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorella","family":"Ilariucci","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Albano","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Lusetti","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3366-1409","authenticated-orcid":false,"given":"Romina","family":"Corsini","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Merli","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Mezzadri","sequence":"additional","affiliation":[{"name":"Azienda USL\u2014IRCCS di Reggio Emilia, 42123 Reggio Emilia, Emilia-Romagna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/bjd.17073","article-title":"Infectious events and associated risk factors in mycosis fungoides\/S\u00e9zary syndrome: A retrospective cohort study","volume":"179","author":"Blaizot","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00289","DOI":"10.1002\/rcr2.289","article-title":"Acute progression of aspergillosis in a patient with lung cancer receiving nivolumab","volume":"6","author":"Uchida","year":"2017","journal-title":"Respirol. Case Rep."},{"key":"ref_3","first-page":"101627","article-title":"A case of non-neutropenic invasive pulmonary aspergillosis under immune checkpoint inhibitor therapy for malignant melanoma","volume":"37","author":"Uchida","year":"2022","journal-title":"Respir. Med. Case Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jama.1992.03480100060031","article-title":"Infections complicating mycosis fungoides and S\u00e9zary syndrome","volume":"267","author":"Axelrod","year":"1992","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S1470-2045(18)30379-6","article-title":"Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): An international, open-label, randomised, controlled phase 3 trial","volume":"19","author":"Kim","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1182\/blood-2014-09-600924","article-title":"Phase 1\/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma","volume":"125","author":"Duvic","year":"2015","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jouandet, M., Nakouri, I., Nadin, L., Kieny, A., Samimi, M., Adamski, H., Qu\u00e9reux, G., Chaby, G., Dompmartin, A., and L\u2019Orphelin, J.M. (2022). Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study. Cancers, 14.","DOI":"10.3390\/cancers14071659"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.2147\/CMAR.S377015","article-title":"Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas","volume":"14","author":"Caruso","year":"2022","journal-title":"Cancer Manag. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1200\/JCO.2011.37.3472","article-title":"Defucosylated anti-CCR4 monoclonal antibody (KW- 0761) for relapsed adult T-cell leukemia\u2013lymphoma: A multi- center phase II study","volume":"30","author":"Ishida","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3324\/haematol.2018.205096","article-title":"Mogamulizumab versus investigator\u2019s choice of chemotherapy regimen in relapsed\/refractory adult T-cell leukemia\/lymphoma","volume":"104","author":"Phillips","year":"2019","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/bjh.13338","article-title":"Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: A randomized phase II study","volume":"169","author":"Ishida","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Drgona, L., Gudiol, C., Lanini, S., Salzberger, B., Ippolito, G., and Mikulska, M. (2018). ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: An infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4). Clin. Microbiol. Infect., 24.","DOI":"10.1016\/j.cmi.2018.03.022"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/intimm\/dxu079","article-title":"CCR4 and its ligands: From bench to bedside","volume":"27","author":"Yoshie","year":"2015","journal-title":"Int. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1084\/jem.191.2.265","article-title":"CC chemokine receptor (CCR)3\/eotaxin is followed by CCR4\/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo","volume":"191","author":"Lloyd","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1096\/fj.02-0193fje","article-title":"Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4mice","volume":"16","author":"Schuh","year":"2002","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bozza, S., Iannitti, R.G., Pariano, M., Renga, G., Costantini, C., Romani, L., and Bayry, J. (2021). Small Molecule CCR4 Antagonists Protect Mice from Aspergillus Infection and Allergy. Biomolecules, 11.","DOI":"10.3390\/biom11030351"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1158\/1078-0432.CCR-14-0830","article-title":"Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive\/refractory mycosis fungoides and S\u00e9zary syndrome","volume":"21","author":"Ni","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/bjd.21018","article-title":"Mogamulizumab induces long-term immune restoration and reshapes tumour heterogeneity in S\u00e9zary syndrome","volume":"186","author":"Roelens","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/00005792-200205000-00005","article-title":"Immune reconstitution inflammatory syndrome: Emergence of a unique syndrome during highly active antiretroviral therapy","volume":"81","author":"Shelburne","year":"2002","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1473-3099(07)70085-3","article-title":"Immune reconstitution syndrome associated with opportunistic mycoses","volume":"7","author":"Singh","year":"2007","journal-title":"Lancet Infect. 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