A1 Refereed original research article in a scientific journal
Wiskott-Aldrich Syndrome: A study on 577 patients defining the genotype as a predictive biomarker for disease severity
Authors: Vallée Tanja C, Glasmacher Jannik S, Buchner Hannes, Arkwright Peter D, Behrends Uta, Bondarenko Anastasia, Browning Michael J, Buchbinder David K, Cattoni Alessandro, Chernyshova Liudmyla, Ciznar Peter, Cole Theresa, Czogala Wojciech, Dueckers Gregor, Edgar John David M, Erbey Fatih, Fasth Anders, Ferrua Francesca, Formankova Renata, Gambineri Eleonora, Gennery Andrew R, Goldman Frederick D, Gonzalez-Granado Luis Ignacio, Heilmann Carsten, Heiskanen-Kosma Tarja, Juntti Hanna, Kainulainen Leena, Kanegane Hirokazu, Karaca Neslihan E., Sebnem Kilic Sara, Klein Christoph, Koltan Sylwia MD PhD, Kondratenko Irina, Meyts Isabelle, Nasrullayeva Gulnara M, Notarangelo Lucia Dora, Pasic Srdjan, Pellier Isabelle, Pignata Claudio, Misbah Siraj Ahmed, Schulz Ansgar S, Segundo Gesmar RS, Shcherbina Anna, Slatter Mary A, Sokolic Robert, Soler-Palacin Pere, Stepensky Polina, van Montfrans Joris M., Ryhänen Samppa, Wolska-Kuśnierz Beata MD PhD, Ziegler John B, Zhao Xiaodong, Aiuti Alessandro, Ochs Hans D, Albert Michael H
Publisher: Elsevier
Publication year: 2024
Journal: Blood
Journal name in source: Blood
Journal acronym: Blood
Volume: 143
Issue: 24
First page : 2504
Last page: 2516
ISSN: 0006-4971
eISSN: 1528-0020
DOI: https://doi.org/10.1182/blood.2023021411
Web address : https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2023021411/515639/Wiskott-Aldrich-Syndrome-A-study-on-577-patients?redirectedFrom=fulltext
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 (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% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot 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 to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
