Refractory immune cytopenia successfully treated with mycophenolate mofetil in four adolescents with del22q11.2 syndrome

Introduction: Chromosome 22q11.2 deletion syndrome (22q11DS) presents a wide variability of phenotypic features, including different grades of immune dysfunctions, leading to increased susceptibility to infections, autoimmune diseases and atopy. The most common autoimmune manifestation in 22q11DS patients is immune thrombocytopenia (ITP), which is often relapsing and refractory to standard therapy. Methods: We present a cohort of four pediatric/adolescents 22q11DS patients presenting with refractory ITP, treated with low dosage Mycophenolate Mofetil (MMF) for more than 24 months. We performed complete deep longitudinal immunological investigations by multiparametric flow cytometry, and monitored blood counts as well as EBV viremia. Results: All four patients didn't experience any relapse since the beginning of MMF therapy. Three out of four showed a complete remission with PLT > 100000/uL. All the patients presented immunological features reported to be associated with immunodysregulation: reduced naïve CD4+T cells and memory B cells, increased cTfh cells and reduced Treg cells frequency. During MMF treatment we detected a decrease in cTfh frequency and a reduction in PD-1 expression along with a moderate recovery of regulatory T cells. Discussion: MMF treatment was associated with sustained platelet stabilization in this cohort. Specific immunological biomarkers could help monitor treatment response, guide clinicians in selecting targeted therapies and may be used to monitor the response to therapy over time.