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.
Front Immunol. 2024 May 30;15:1415389. doi: 10.3389/fimmu.2024.1415389. eCollection 2024.
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; = 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, = 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; = 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.
简介：自身免疫性血细胞减少症（AIC）是一组以免疫介导的血细胞破坏为特征的疾病。在儿童中，它们通常继发于免疫失调，可能需要长期免疫抑制治疗。霉酚酸酯和西罗莫司是两种耐受性良好的治疗这些疾病的选择，通常作为类固醇保留治疗。然而，对于接受长期治疗的患者，尚无关于感染风险的数据。
患者和方法：通过分析 2015 年 1 月至 2023 年 7 月期间在意大利两个大型儿科血液学中心接受霉酚酸酯或西罗莫司治疗的孤立性 AIC 或与自身免疫性淋巴组织增生综合征（ALPS）/ALPS 样综合征相关的 AIC 的住院病历，计算每 100 人/月风险（p/m/r）的严重感染事件发生率。
结果：2015 年 1 月至 2023 年 7 月，96 例接受霉酚酸酯或西罗莫司治疗的患者中有 13 例发生 16 例需要住院的严重感染事件。没有患者死亡。总体感染率为 0.24 人/*100 个月/risk（95%CI 0.09-0.3）。与其他患者相比，ALPS 样患者的严重感染事件发生率更高（0.42 比 0.09； = 0.006），而与霉酚酸酯治疗相比，开始西罗莫司治疗的患者感染率更低（0.04 比 0.29， = 0.03）。仅考虑在研究开始时开始治疗的患者，60 个月时总体累积风险为 18.6%（95%CI 3.4-31.4），ALPS 样患者 5 年后发生感染事件的风险更高（26.1%；95%CI 3.2-43.5）与其他 AIC 患者（4%；95%CI 0-11.4； = 0.041）。
讨论：据我们所知，这是第一项描述与 AIC 和免疫失调患者使用霉酚酸酯和西罗莫司慢性治疗相关的感染风险的研究。我们的数据表明，感染率非常低，主要与潜在的血液学状况有关。
结论：霉酚酸酯和西罗莫司是 AIC 和免疫失调综合征的一种安全的免疫抑制治疗方法。
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