{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:09:31Z","timestamp":1792796971116,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autoimmune cytopenias (AICs) are a group of disorders characterized by immune-mediated destruction of blood cells. In children, they are often secondary to immune dysregulation that may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well-tolerated options to treat these disorders, often as a steroid-sparing option. However, no data are available on the infection risk for patients undergoing long-lasting treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>The rate of severe infective events was calculated in episodes per 100 persons\/months at risk (p\/m\/r) documented by the analysis of hospitalization charts between January 2015 and July 2023 of patients treated with mycophenolate mofetil or sirolimus given for isolated AIC or AICs associated with autoimmune lymphoproliferative syndrome (ALPS)\/ALPS-like syndromes in two large Italian pediatric hematology units.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From January 2015 to July 2023, 13 out of 96 patients treated with mycophenolate mofetil or sirolimus developed 16 severe infectious events requiring hospitalization. No patients died. Overall infection rate was 0.24 person\/*100 months\/risk (95% CI 0.09\u20130.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; <jats:italic>p<\/jats:italic> = 0.006) and lower in patients who underwent mycophenolate treatment alone compared to those who started sirolimus after mycophenolate failure (0.04 versus 0.29, <jats:italic>p<\/jats:italic> = 0.03). Considering only patients who started treatment at the beginning of study period, overall cumulative hazard was 18.6% at 60 months (95% CI 3.4\u201331.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2\u201343.5) compared to other AICs (4%; 95% CI 0\u201311.4; <jats:italic>p<\/jats:italic> = 0.041).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>To the best of our knowledge, this is the first study to describe the infectious risk related to mycophenolate and sirolimus chronic treatment in patients with AICs and immune dysregulation. Our data highlight that infection rate is very low and mainly related to the underlying hematological condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1415389","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T05:59:00Z","timestamp":1717048740000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus"],"prefix":"10.3389","volume":"15","author":[{"given":"Mattia","family":"Comella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Palmisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Mariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Dell\u2019Orso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Licciardello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carla","family":"Giarratana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Arcuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pestarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Lanciotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Brucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Guardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Dufour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fioredda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Castagnola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Miano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13533","article-title":"Mycophenolate mofetil and Sirolimus as second or further line treatment in children with chronic refractory Primitive or Secondary Autoimmune Cytopenias: A single centre experience","volume":"171","author":"Miano","year":"2015","journal-title":"Br J Haematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100822","article-title":"Immune thrombocytopenia: A review of upfront treatment strategies","volume":"49","author":"Kochhar","year":"2021","journal-title":"Blood Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000812","article-title":"Updated international consensus report on the investigation and management of primary immune thrombocytopenia","volume":"3","author":"Provan","year":"2019","journal-title":"Blood Adv"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-162503","article-title":"Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: Report from an international working group","volume":"113","author":"Rodeghiero","year":"2009","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000966","article-title":"American Society of Hematology 2019 guidelines for immune thrombocytopenia","volume":"3","author":"Neunert","year":"2019","journal-title":"Blood Adv"},{"key":"B6","article-title":"Recommendations for the management of acute immune thrombocytopenia in children. 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