Cohen A R, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F
Children's Hospital of Philadelphia, Philadelphia, PA, USA; Istituto di Clinica e Biologia Dell'Eta'Evolutiva, Cagliari, Italy.
Br J Haematol. 2000 Feb;108(2):305-12. doi: 10.1046/j.1365-2141.2000.01866.x.
In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
在以往的试验中，口服活性铁螯合剂去铁酮（L1）与散发性粒细胞缺乏症、较轻形式的中性粒细胞减少症及其他副作用有关。为确定这些事件的发生率，我们对该螯合剂进行了一项多中心前瞻性研究。每周进行血常规检查，确诊为中性粒细胞减少症则必须停药。在187例重型地中海贫血患者中，粒细胞缺乏症（中性粒细胞<0.5×10⁹/L）的发生率为0.6/100患者年，较轻形式的中性粒细胞减少症（中性粒细胞0.5 - 1.5×10⁹/L）的发生率为5.4/100患者年。所有中性粒细胞减少症病例在治疗中断后均得到缓解。中性粒细胞减少症主要发生在未行脾切除术的患者中。恶心和/或呕吐在治疗早期出现，通常为一过性，有3例患者因之停用去铁酮。轻至中度关节疼痛和/或肿胀无需永久停用去铁酮，且更常见于铁蛋白水平较高的患者。治疗期间平均丙氨酸转氨酶（ALT）水平升高。ALT水平升高一般为一过性，更常见于丙型肝炎患者。免疫学研究持续变化不常见，尽管散发性异常很常见。治疗期间平均锌水平下降。总体组中铁蛋白水平未改变，但基线水平>2500微克/升的患者中铁蛋白水平下降。本研究描述了去铁酮的安全性概况，并在特定监测条件下表明，粒细胞缺乏症比先前预测的少见。
