Platzbecker U, Haase M, Herbst R, Hänel A, Voigtmann K, Thiede C H, Mohr B, Schleyer E, Leopold T, Orth M, Hänel M, Ehninger G, Bornhäuser M
Medizinische Klinik und Poliklinik I des Universitätsklinikum Carl Gustav Carus Dresden, 01307 Dresden, Germany.
Br J Haematol. 2005 Mar;128(5):625-30. doi: 10.1111/j.1365-2141.2005.05360.x.
The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7 months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria. Major side-effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.
骨髓增生异常综合征（MDS）的病理生理学涉及血管生成、细胞凋亡、增殖与分化以及免疫监视的调节紊乱。越来越多的数据表明，西罗莫司可能对这些途径产生积极影响，因此可能对该病患者具有治疗益处。19例诊断为MDS的患者，中位年龄72岁（范围54 - 80岁），口服西罗莫司，目标血药浓度为3 - 12 ng/ml。西罗莫司给药中位时间为3.7个月（范围0.3 - 11个月）。根据国际工作组标准，3例患者[1例伴过多原始细胞的难治性贫血（RAEB）- 2、1例RAEB - 1、1例伴有多系发育异常的难治性血细胞减少症]显示出主要（1例血小板、1例中性粒细胞）或次要（1例红系、2例血小板）血液学反应。主要副作用为高脂血症（n = 4）、口腔炎（n = 3）、血小板减少症（n = 2）和尿路感染（n = 1）。这些数据表明，西罗莫司对部分病情更严重的MDS患者有活性。
