Document Detail


X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.
MedLine Citation:
PMID:  20173115     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.
Authors:
Michael H Albert; Tanja C Bittner; Shigeaki Nonoyama; Lucia Dora Notarangelo; Siobhan Burns; Kohsuke Imai; Teresa Espanol; Anders Fasth; Isabelle Pellier; Gabriele Strauss; Tomohiro Morio; Benjamin Gathmann; Jeroen G Noordzij; Cristina Fillat; Manfred Hoenig; Michaela Nathrath; Alfons Meindl; Philipp Pagel; Uwe Wintergerst; Alain Fischer; Adrian J Thrasher; Bernd H Belohradsky; Hans D Ochs
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2010-02-19
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-05-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3231-8     Citation Subset:  AIM; IM    
Affiliation:
Dr von Haunersches Kinderspital, Ludwig-Maximilians-Universit?t, Munich, Germany. michael.albert@med.lmu.de
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Autoimmune Diseases / epidemiology,  etiology
Child
Child, Preschool
Disease-Free Survival
Female
Genes, X-Linked
Hemorrhage / epidemiology,  etiology
Humans
Incidence
Infection / epidemiology,  etiology
Kaplan-Meiers Estimate
Male
Middle Aged
Mutation
Neoplasms / epidemiology,  etiology
Phenotype
Retrospective Studies
Thrombocytopenia / complications*,  genetics,  mortality*
Wiskott-Aldrich Syndrome Protein / genetics*
Young Adult
Chemical
Reg. No./Substance:
0/Wiskott-Aldrich Syndrome Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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