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Article

PubMed

This record comes from PubMed

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

Blood. 2024 Jun 13 ; 143 (24) : 2504-2516.

ISSN 1528-0020 | 0006-4971
Source

Language English Country United States Media print

Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid38579284

PubMed 38579284
DOI 10.1182/blood.2023021411
PII: 515639
Knihovny.cz E-resources

MeSH
Biomarkers MeSH
Child MeSH
Adult MeSH
Genotype * MeSH
Infant MeSH
Middle Aged MeSH
Humans MeSH
Survival Rate MeSH
Adolescent MeSH
Young Adult MeSH
Follow-Up Studies MeSH
Child, Preschool MeSH
Prognosis MeSH
Wiskott-Aldrich Syndrome Protein genetics MeSH
Retrospective Studies MeSH
Severity of Illness Index MeSH
Hematopoietic Stem Cell Transplantation MeSH
Wiskott-Aldrich Syndrome * genetics diagnosis therapy MeSH
Check Tag
Child MeSH
Adult MeSH
Infant MeSH
Middle Aged MeSH
Humans MeSH
Adolescent MeSH
Young Adult MeSH
Male MeSH
Child, Preschool MeSH
Female MeSH
Publication type
Journal Article MeSH
Multicenter Study MeSH
Research Support, Non-U.S. Gov't MeSH
Names of Substances
Biomarkers MeSH
Wiskott-Aldrich Syndrome Protein MeSH

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.

Allergy and Immunology Division Pediatrics Department Universidade Federal de Uberlândia Uberlândia Brazil

Azerbaijan Medical University Baku Azerbaijan

Bone Marrow Transplantation Department Hadassah Hebrew University Medical Center Jerusalem Israel

Centre de référence des déficits immunitaires primitifs CEREDIH CHU d'Angers Angers France

Children's Hospital School of Medicine Technical University Munich Munich Germany

Children's Hospital University of Helsinki and Helsinki University Hospital Pediatric Research Center Helsinki Finland

Clinical Immunology John Radcliffe Hospital Oxford United Kingdom

Department for Children and Adolescents Pediatric Hematopoietic Stem Cell Transplantation and Immunodeficiency Copenhagen University Hospital Rigshospitalet København Denmark

Department of Allergy and Immunology The Royal Children's Hospital Melbourne Australia

Department of Child Health and Development Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan

Department of Haematology Oncology Anna Meyer University Children's Hospital Florence Italy

Department of Hematology Children's Hospital of Orange County Orange CA