Bone Marrow Transplantation as a Method of Choice in Treatment of Gain-of-Function Mutations in STAT1. Case Report

Abstract

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) was described. This disease is often accompanied by severe immunodeficiency. In the treatment of such patients, antifungal, antibacterial therapy is used, which is not always effective. Some patients underwent bone marrow transplantation with various efficacy. The indications for bone marrow transplantation in this pathology remain uncertain. This causes difficulties for doctors and patients in making the choice of bone marrow transplantation. In this paper, we present a case of successful peripheral blood stem cell transplantation in a patient with gain-of-function mutations in STAT1. A boy at the age of 1 year and 8 months with gain-of-function mutations in STAT1 had a recurrent course of candidial infection (esophagitis, stomatitis), repeated lung lesions, repeated pneumonia with a poor or short-term response to antifungal and antibacterial drugs. Recurrent infections led to delay in physical development. Cellular immunodeficiency (decrease of CD4+ T-lymphocytes) was identified. The inexorable course of the infectious syndrome, deterioration of the quality of life of the patient and his family led to the decision to undergo bone marrow transplantation on demand of the child’s parents. The possible favorable prognostic factors for successful bone marrow transplantation were early age, presence of gain-of-function mutations in the STAT1 mutation variant, and a related donor. The patient has survived. However, there were complications during the transplantation in the form of acute and then chronic graft-versus-host disease (GvHD). There was the reconstitution of immunity, the infectious process did not manifest. The patient has become active; at this time, he does not differ in his physical development from his peers. The decision to carry out transplantation should be made individually, based on the severity of immunodeficiency, desire of parents, and presence of possible favorable factors in a patient.