Late-onset hemophagocytic lymphohistiocytosis associated with monoallelic STX11 mutation in an adult: a case report and rationale for early allogeneic hematopoietic cell transplantation.

Abstract

Late-onset familial hemophagocytic lymphohistiocytosis (fHLH) remains a diagnostic and therapeutic challenge, particularly in adult patients presenting without a clear family history. We report a fatal case of HLH in a previously healthy adult harboring a monoallelic STX11 mutation. The patient presented with progressive jaundice, persistent high-grade fever, and pancytopenia, and was unresponsive to HLH-2004 protocol therapy with etoposide and dexamethasone, as well as subsequent salvage regimens. Despite aggressive treatment, the disease remained refractory, ultimately resulting in multi-organ failure. This case, alongside a review of reported adult-onset fHLH cases, highlights the diagnostic value of early genetic testing in adults with unexplained HLH, especially after secondary causes have been ruled out. Our findings underscore the importance of timely consideration of underlying genetic predisposition, even in the absence of biallelic mutations or childhood onset. Given the poor response to conventional therapies, early referral for allogeneic hematopoietic cell transplantation should be prioritized in suspected or confirmed fHLH cases to improve survival outcomes.