Sirolimus as Successful Treatment in Children with Chronic/Refractory Primary Autoimmune Hemolytic Anemia

Introduction Autoimmune hemolytic anemia (AIHA) is a rare disorder that can follow a chronic/refractory course. Therapeutic management beyond first-line steroids remains challenging in children. Different immunosuppressive agents have been used as second/further-line treatments. Data supporting the use of sirolimus are limited to patients with autoimmune lymphoproliferative syndrome (ALPS) and Evans syndrome (ES). Methods We conducted a retrospective single-center study including children with chronic/refractory AIHA treated with sirolimus in our center. Patients with a diagnosis of ALPS or ES were excluded. Complete response (CR) and partial response (PR) were defined as the normalization of hemoglobin levels according to age-adjusted reference values, with the absence of clinical signs of hemolysis and as the sustained increase in hemoglobin of ≥2 g/dL from baseline, reduced transfusion requirements, and persistence of minor signs of hemolysis, respectively. No response was defined as the absence of clinical and laboratory improvement, requiring additional therapies. Results Between 2002 and 2025, 15 patients (8 males, 7 females) with a median age at disease onset of 4.3 years (range 0.1–16.1) were included. AIHA was isolated in 60% of cases. The remaining patients presented signs of immune dysregulation. Median hemoglobin levels at diagnosis were 5.6 g/dL (range 2.1–11.3). Sirolimus was initiated after a median of 341 days from diagnosis and was used as second (5) or further-line (10) therapy. Steroids were given as first-line therapy in all cases. All patients achieved a response, which was complete and partial in 13 (87%) and 2 (13%) cases, respectively. Median follow-up was 6.4 years (range 2–23). Six patients experienced a disease relapse, successfully managed with steroid reintroduction, sirolimus reinitiation, or dose adjustment in all cases. Sirolimus was ongoing in 6 patients at the last follow-up. Adverse events were observed in 11 patients and consisted of dyslipidemia (4), infections (3), ovarian cysts (2), mild transaminase elevation (1), and oral aphthosis (1). No patients needed to discontinue the therapy due to toxicity. Conclusions Sirolimus proved to be an effective therapeutic option for children with chronic/refractory AIHA other than ALPS and ES. These findings support its role as a valuable treatment in this complex patient population.