Comorbidities in Mild WAS/XLT Require Lifelong Follow-Up and Consideration of Definitive Treatment.

Abstract

Loss of function mutations in the gene encoding WASP (Wiskott-Aldrich syndrome protein) result in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia-XLT (WAS/XLT). The clinical severity of the disease can be assessed using the WAS clinical severity score. Typically, patients with a score of 3 or less at 2 years of age are considered to have mild WAS/XLT disease. However, patients with a low score in the first 2 years of life can still experience life-threatening complications, and there are no agreed guidelines for the management of these patients with mild WAS/XLT. We analyzed data on WAS/XLT patients from the French National Reference Centre for Primary Immunodeficiencies registry. At 10 December 2021, data were available for 261 patients, 170 of whom had mild WAS/XLT. The median age of these patients at last follow-up was 15.8 years (range 2.0-60.4). Overall survival at 40 years was 73% in mild WAS patients versus 65% in severe WAS patients (p = 0.43). In the mild WAS population, prior to Hematopoietic Stem Cell Transplantation or gene therapy, 38.2% of patients progressed to a WAS severity score of 4-5 after the age of 2. Remarkably, no deaths were reported in 45 HSCTs performed since 2010, regardless of initial severity, type and HLA compatibility of the transplant, and age at diagnosis, with a median follow-up of 3.2 years (0-11.5) after transplant. As complications can occur throughout life, our study supports definitive treatment for all patients when available, including those with mild forms.