Dr von Haunersches Kinderspital, Ludwig-Maximilians-Universität, Munich, Germany.
Blood. 2010 Apr 22;115(16):3231-8. doi: 10.1182/blood-2009-09-239087. Epub 2010 Feb 19.
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.
很大一部分患有 Wiskott-Aldrich 综合征（WAS）蛋白基因突变的患者表现出较轻的表型，称为 X 连锁血小板减少症（XLT）。虽然干细胞移植是治疗 WAS 患者的首选方法，但 XLT 患者的治疗选择存在争议。在一项回顾性多中心研究中，我们定义了 XLT 的临床表型，并确定了在有记录的 WAS 基因突变且患有轻度至中度湿疹或轻度、偶发性感染的 2 岁以上患者中，严重疾病相关并发症的概率。共有来自 12 个国家的 173 名患者（中位年龄 11.5 岁）入组，随访时间为 2830 患者年。13.9%的患者发生严重出血事件，6.9%的患者发生危及生命的感染，12.1%的患者发生自身免疫，5.2%的患者发生恶性肿瘤。突变类型、静脉注射免疫球蛋白或抗生素预防对总生存和无事件生存概率没有显著影响。脾切除术导致严重感染风险增加。对 XLT 患者的临床结果和分子基础进行的这项分析表明，患者具有极好的长期生存，但也存在较高的严重疾病相关并发症的概率。这些观察结果将有助于在为 XLT 患者考虑治疗方案时做出更好的决策。
