Refractory autoimmune cytopenia in children, possible role for sirolimus treatment

Abstract Background In autoimmune cytopenias (AC), the immune system destroys one or more hematopoietic lineage cells. Children with multilineage autoimmune cytopenias often experience chronic, therapy-refractory illness, unlike those with single-lineage autoimmune cytopenias. Unfortunately, few long-term, well-tolerated treatments are available. Sirolimus possesses properties that make it a promising and tolerable agent for refractory autoimmune cytopenias. Aim of the study This study aimed to profile and analyze the laboratory and clinical features of refractory autoimmune cytopenia in children and determine the role of sirolimus in improving outcomes. Methods Twenty-two patients with refractory autoimmune cytopenia were included. Each patient underwent detailed history-taking and thorough clinical examination. Sirolimus was administered to patients refractory to first-line therapy and assessed for response, relapse, or progression over a minimum of three months. Results An underlying inborn error of immunity (IEI) was identified in 14 patients (63.63%) with refractory cytopenia. Cases with IEI were more likely to have Evan syndrome and lymphoproliferation, such as hepatosplenomegaly (HSM) or lymphadenopathy. The initial response rate to sirolimus was 63.64%, and at study completion, it was 54.54%. Responders were more likely to have underlying IEI ( P = 0.008) and autoimmune hemolytic anemia rather than isolated thrombocytopenia ( P < 0.001). Age, sex, time from diagnosis to sirolimus administration, number and type of previous medications, response to prior therapies, and serum sirolimus concentration did not significantly differ between responders and non-responders. Conclusion Sirolimus showed potential as a treatment for children with refractory cytopenia, particularly those presenting with AIHA and underlying inborn errors of immunity, demonstrating an acceptable safety profile. However, additional research with larger cohorts and longer follow-up time is needed to confirm these results.