Fisher-Evans Syndrome in Children: an Analysis of Genetic Defects and Therapy Response

Abstract

The Fisher–Evans syndrome (FES), also known as Evans syndrome (ES) is an immune hemopathy characterized by bicytopenia or pancytopenia in the absence of other diseases. FES may be either primary/idiopathic, or secondary, occurring against the background of other diseases. In children, FES is frequently related to a primary immunodeficiency disorder (PID). This article presents a retrospective data analysis of a cohort of pediatric patients (n = 14) with FES, the aim of which is to demonstrate the necessity of conducting a molecular genetic investigation for PID diagnosis. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The patients from this cohort were presented at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology during the period 2012–2019. All of these patients underwent Next Generation Sequencing (NGS). The median age of disease onset was 5.5 years (from 5 months to 16 years). The male-to-female ratio was 1.8:1. Thanks to the results of the genetic investigation conducted on 14 patients with FES, it was possible to identify 10 children (71.4%) who had secondary FES. The median age of disease onset in patients with secondary FES was 4 years, the minimum age was 5 months, the maximum age was 12 years. The male-to-female ratio was 7:3. Most frequently, the disease onset was associated with ITP, immune thrombocytopenia (35.7% of patients) or simultaneously with ITP and AIHA, autoimmune hemolytic anemia (35.7% of patients); less frequently, the disease onset was associated with AIHA, with a subsequent occurrence of ITP (21.4% of patients). A pancytopenia was identified in 1 patient with FES associated with a PID. Among our patients with a disease onset associated with AIHA, there was not a single case with a PID. We noted an extremely low effectiveness of glucocorticoids and IVIgs for the treatment of FES: in practically 100% of cases, the patients in the analysed group required second and subsequent lines of therapy. Among other therapy types, effective for both primary and secondary FES, we should note rituximab (62% of patients stay in remission for up to 1 year) and MMF (80% of patients stay in remission for up to 1 year). On the basis of the conducted study we can conclude that male patients with FES under 18 years of age whose disease onset was associated with ITP need to be thoroughly tested for PID, including genetic testing, since patients in this group have the greatest PID incidence. Treating FES with glucocorticoids and IVIgs is nearly always not very effective and second and subsequent lines of therapy are required. The drugs of choice which are most effective for patients with FES are rituximab and MMF.