Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.

Autor:	Comella M; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; Pediatric Hematology and Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy., Palmisani E; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Mariani M; Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy., Dell'Orso G; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Licciardello M; Pediatric Hematology and Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy., Giarratana MC; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Arcuri L; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Pestarino S; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Grossi A; Genetic and Genomic of Rare Disease Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy., Lanciotti M; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Brucci G; Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy., Guardo D; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Russo G; Pediatric Hematology and Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy., Dufour C; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Fioredda F; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Castagnola E; Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy., Miano M; Haematology Unit, Department of Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 May 30; Vol. 15, pp. 1415389. Date of Electronic Publication: 2024 May 30 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1415389
Abstrakt:	Introduction: 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. Patients and Methods: 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. Results: 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 0.09-0.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; p = 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, p = 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 3.4-31.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2-43.5) compared to other AICs (4%; 95% CI 0-11.4; p = 0.041). Discussion: 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. Conclusions: Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Comella, Palmisani, Mariani, Dell’Orso, Licciardello, Giarratana, Arcuri, Pestarino, Grossi, Lanciotti, Brucci, Guardo, Russo, Dufour, Fioredda, Castagnola and Miano.)
Databáze:	MEDLINE
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