Long-Term Outcomes of Successful Treatment with Ruxolitinib in a Pediatric Patient with Autoimmune Lymphoproliferative Syndrome and a Signal Transducer and Activator of Transcription 3 Gain-of-Function Mutation.

Loss or gain-of-function mutations in signal transducer and transcription activator genes, classified as combined immunodeficiency, can present with highly heterogeneous and life-threatening clinical presentations. We report an adolescent girl who has combined immunodeficiency associated with signal transducer and activator of transcription 3 gain-of-function, c.1032G > C, p.Met344Ile located in exon 10, identified by a next-generation sequencing panel performed due to short stature, hepatosplenomegaly, and decreased levels of both immunoglobulin G and immunoglobulin M. At 12 years of age, the patient was referred to the pediatric hematology outpatient clinic owing to hepatosplenomegaly and pancytopenia after initiating growth hormone treatment due to short stature. On physical examination, bilateral multiple posterior and anterior cervical micro-lymphadenopathies were detected, her liver was palpated 6 cm below the costal margin, and her spleen was palpated 10 cm below the costalmargin. The whole blood count revealed a leukocyte count of 2,300/mm3, neutrophils of 1,330/mm3, lymphocytes of 730/mm3, hemoglobin of 8 g/dL, platelets of 96,000/mm3, and reticulocytes of 2%. The bone marrow biopsy revealed a cellularity of 30-35%. After steroid-dependent treatment resulted in Cushing syndrome and treatment with sirolimus was ineffective, treatment with ruxolitinib 20 mg twice daily significantly resolved cytopenias and hepatosplenomegaly due to autoimmune lymphoproliferative syndrome.