Infection risk of Mycophenolate Mofetil and Sirolimus treatments in patients with Autoimmune Cytopenias and Primary Immuno-Regulatory Disorders.

Introduction. Autoimmune cytopenias are a group of disorders characterized by immune-mediated destruction of blood cells. In children they are often secondary to immune dysregulation which may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well tolerated options to treat these disorders, often used for steroid-dependent patients. However, no data are available on the infection risk for patients undergoing long-lasting treatments. Patients and Methods. A retrospective data review of patients suffering from Primary Immuno-Regulatory Disorders, mainly ALPS/ALPS-like syndromes, and immune thrombocytopenia treated with Mycophenolate and Sirolimus at Haematology Unit of G. Gaslini Children’s Hospital and Pediatric Hematology and Oncology Unit of the Policlinico of Catania have been performed on patients’ clinical charts. Moreover, an exhaustive search was performed on the main scientific libraries including PubMed, Embase, Google Scholar and Cochrane. Results. From January 2015 to May 2023, 13 out of 112 patients (11%) undergoing treatment with mycophenolate mofetil or sirolimus developed severe infections requiring hospitalization. No patients died. Infections involved 11 out of 69 (15%) and 2 of 91 (2%) patients treated with sirolimus and mycophenolate, respectively. The infection rate under sirolimus therapy was significantly higher in patients with ALPS-like syndromes (9, 13%) than in patients with ALPS and immune thrombocytopenia (2, 2%) (p=0.007); moreover, infection rate was higher in 1 patients who sequentially received both therapies (8, 61%) (p=0.03) and was significantly correlated with therapy duration (p=0.04). Infectious events free survival was 98%, over 12 months, 95% over 36 months, 93% over 60 months and 90% over 72 months. Discussion To the best of our knowledge, this is the first study describing the infectious risk related to mycophenolate and sirolimus treatments in patients with autoimmune cytopenias and immune-dysregulation. It highlights that the infections rate is rather low and mainly related to the underlying condition. Conclusions Mycophenolate and sirolimus represent a safe immunosuppressive therapy in autoimmune cytopenias and syndrome with immune dysregulation.