The outcome of haematopoietic stem cell transplantation in a patient with STAT1 gain-of-function: a case report

Background: The human signal transducer and activator of transcription 1 (STAT1) is a latent cytoplasmic transcription factor and one of seven members of the STAT family. Autosomal dominant (AD) STAT1 gain-of-function (GOF), characterized by enhanced phosphorylation of the tyrosine-701 residue and STAT1 activation, is commonly associated with chronic mucocutaneous candidiasis (CMCC), immunodeficiency, aneurysms, malignancies, and autoimmune phenomena. The best management strategies for patients with STAT1 GOF remain unclear. Typically, the standard care includes supportive treatments such as antimicrobial prophylaxis, either alone or combined with immunoglobulin replacement therapy. Biological therapies such as JAK inhibitors have been shown to alleviate symptoms of infection and autoimmune disorders in patients with STAT1 GOF mutations. However, there is a lack of long-term outcome data for JAK inhibition. Hematopoietic stem cell transplantation (HSCT) is an alternative treatment option for a subset who experience a persistent disease course despite conventional therapy. However, the effectiveness of HSCT for this condition is not yet well established. Methods: Our patient’s medical records were analyzed retrospectively, including her medical history. Results: We present the outcome of HSCT performed on a 27-year-old female with STAT1 GOF, conducted as a treatment for acute myeloid leukemia (AML). Conclusion: HSCT may serve as an alternative and potentially curative treatment for certain STAT1 GOF patients with progressive, life-threatening conditions that do not respond to conventional therapies. Additional research is needed to improve the management of these patients. Statement of Novelty: We present a novel case study of HSCT as a treatment for AML in a 27-year-old patient with STAT1 GOF, highlighting the potential for curative outcomes in progressive, life-threatening conditions unresponsive to conventional therapies. This case contributes to the limited body of evidence supporting the efficacy and challenges of HSCT in STAT1 GOF patients.