Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York] : Elsevier
      Original Publication: New York, Grune & Stratton [etc.]
    • Subject Terms:
      Wiskott-Aldrich Syndrome*/genetics ; Wiskott-Aldrich Syndrome*/diagnosis ; Wiskott-Aldrich Syndrome*/therapy ; Genotype*; Humans ; Adolescent ; Child ; Male ; Female ; Child, Preschool ; Adult ; Retrospective Studies ; Infant ; Young Adult ; Biomarkers ; Hematopoietic Stem Cell Transplantation ; Severity of Illness Index ; Wiskott-Aldrich Syndrome Protein/genetics ; Follow-Up Studies ; Middle Aged ; Prognosis ; Survival Rate
    • Abstract:
      Abstract: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.
    • Comments:
      Comment in: Blood. 2024 Jun 13;143(24):2447-2448. doi: 10.1182/blood.2024024563. (PMID: 38869923)
    • Accession Number:
      0 (Biomarkers)
      0 (Wiskott-Aldrich Syndrome Protein)
    • Publication Date:
      Date Created: 20240405 Date Completed: 20240613 Latest Revision: 20241104
    • Publication Date:
      20241105
    • Accession Number:
      10.1182/blood.2023021411
    • Accession Number:
      38579284