X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.
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.
Albert
Michael H
MH
Dr von Haunersches Kinderspital, Ludwig-Maximilians-Universität, Munich, Germany. michael.albert@med.lmu.de
Bittner
Tanja C
TC
Nonoyama
Shigeaki
S
Notarangelo
Lucia Dora
LD
Burns
Siobhan
S
Imai
Kohsuke
K
Espanol
Teresa
T
Fasth
Anders
A
Pellier
Isabelle
I
Strauss
Gabriele
G
Morio
Tomohiro
T
Gathmann
Benjamin
B
Noordzij
Jeroen G
JG
Fillat
Cristina
C
Hoenig
Manfred
M
Nathrath
Michaela
M
Meindl
Alfons
A
Pagel
Philipp
P
Wintergerst
Uwe
U
Fischer
Alain
A
Thrasher
Adrian J
AJ
Belohradsky
Bernd H
BH
Ochs
Hans D
HD
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D050172:Genes, X-Linked; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D010641:Phenotype; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000150:complications* / Q000235:genetics / Q000401:mortality*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*; D055815:Young Adult
D051316:Wiskott-Aldrich Syndrome Protein