How I treat Wiskott-Aldrich syndrome.

Abstract

Abstract: Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder, characterized by thrombocytopenia, eczema, recurrent infections, autoimmunity, and malignancy. Here, we discuss current conservative and definitive approaches to treating WAS, based on recently published evidence. Disease severity in WAS is highly variable. Recent studies confirm that the probability of disease progression depends on the type of genetic variant, supporting early diagnosis and tailored treatment strategies. Milder cases, historically termed X-linked thrombocytopenia (XLT), received supportive care, whereas severe cases were referred for standard allogeneic hematopoietic cell transplantation (HCT) or gene therapy (GT) in clinical trials. Advances in HCT and GT, together with recent knowledge that even patients with XLT are at risk for severe immune complications, suggest that most young patients with WAS should be offered a potentially curative approach at diagnosis. Older patients with a small subset of milder variants may be treated conservatively unless they develop life-threatening autoimmune or malignant complications; regular monitoring and proactive management are critical to preventing irreversible complications. We recommend discontinuing the term XLT as it implies a mild and uncomplicated disease, which is not the norm, and instead tailor treatment for all patients with WAS to their individual genetic profile, disease severity, and clinical course.