X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options

被引:144
作者
Albert, Michael H. [1 ]
Bittner, Tanja C. [1 ]
Nonoyama, Shigeaki [2 ]
Notarangelo, Lucia Dora [3 ]
Burns, Siobhan [4 ]
Imai, Kohsuke [2 ]
Espanol, Teresa [5 ]
Fasth, Anders [6 ]
Pellier, Isabelle [7 ]
Strauss, Gabriele [8 ]
Morio, Tomohiro [9 ]
Gathmann, Benjamin [10 ]
Noordzij, Jeroen G. [11 ]
Fillat, Cristina [12 ]
Hoenig, Manfred [13 ]
Nathrath, Michaela [14 ]
Meindl, Alfons [15 ]
Pagel, Philipp [16 ]
Wintergerst, Uwe [17 ]
Fischer, Alain [18 ]
Thrasher, Adrian J. [4 ]
Belohradsky, Bernd H. [1 ]
Ochs, Hans D. [19 ]
机构
[1] LMU, Dr Von Haunerschen Kinderspital, D-80337 Munich, Germany
[2] Natl Def Med Coll, Tokorozawa, Saitama, Japan
[3] Univ Brescia, Brescia, Italy
[4] UCL, Inst Child Hlth, London, England
[5] Vall Hebron Hosp, Barcelona, Spain
[6] Queen Silvia Childrens Hosp, Gothenburg, Sweden
[7] CHU Angers, Angers, France
[8] Otto Heubner Zentrum Kinder & Jugendmed, Charite Campus Virchow Klinikum, Berlin, Germany
[9] Tokyo Med & Dent Univ, Tokyo, Japan
[10] Univ Freiburg Klinikum, Freiburg, Germany
[11] St Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands
[12] Ctr Invest Biomed Red Enfermedades Raras, Ctr Regulacio Genom, Barcelona, Spain
[13] Univ Klin Kinder & Jugendmed Ulm, Ulm, Germany
[14] Tech Univ Munich, Univ Childrens Hosp, Munich, Germany
[15] Tech Univ Munich, Frauenklin, Klinikum Rechts Isar, Munich, Germany
[16] Tech Univ, Lehrstuhl Genomorientierte Bioinformat, Wissensch Zentrum Weihenstephan, Freising Weihenstephan, Germany
[17] Krankenhaus St Josef, Braunau, Austria
[18] Hop Necker Enfants Malad, Paris, France
[19] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA
关键词
WISKOTT-ALDRICH-SYNDROME; BONE-MARROW-TRANSPLANTATION; SYNDROME PROTEIN GENE; WASP; SPLENECTOMY; AUTOIMMUNITY; EXPRESSION; MANAGEMENT; THERAPY;
D O I
10.1182/blood-2009-09-239087
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood. 2010; 115(16): 3231-3238)
引用
收藏
页码:3231 / 3238
页数:8
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