Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria
Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria
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DOI：
10.1056/nejmoa031688
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发表时间：
2004-02-05
影响因子：
158.5
通讯作者：
Rother, RP
中科院分区：
文献类型：
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作者：
Hillmen, P;Hall, C;Rother, RP
背景：阵发性夜间血红蛋白尿（PNH）是由造血干细胞中猪- a基因的体细胞突变引起的，随后产生的血细胞缺乏保护细胞免受补体系统攻击的表面蛋白。我们测试了eculizumab的临床疗效，eculizumab是一种抑制终末补体成分激活的人源化抗体，用于PNH患者。方法：11例输注依赖的PNH患者每周输注eculizumab (600 mg)，持续四周，一周后再输注900 mg，然后每隔一周输注900 mg，直到第12周。在整个试验过程中测量溶血的临床和生化指标。结果：平均乳酸脱氢酶水平从治疗前的3111 IU / l下降到治疗期间的594 IU / l （P=0.002）。PNH III型红细胞的平均百分比从36.7%增加到59.2% （P=0.005）。平均输血率和中位数输血率分别从每个患者每月2.1和1.8个单位下降到每个患者每月0.6和0.0个单位（中位数率比较P=0.003）。血红蛋白尿发作减少96% (P
Background: Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and the subsequent production of blood cells with a deficiency of surface proteins that protect the cells against attack by the complement system. We tested the clinical efficacy of eculizumab, a humanized antibody that inhibits the activation of terminal complement components, in patients with PNH.Methods: Eleven transfusion-dependent patients with PNH received infusions of eculizumab (600 mg) every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12. Clinical and biochemical indicators of hemolysis were measured throughout the trial.Results: Mean lactate dehydrogenase levels decreased from 3111 IU per liter before treatment to 594 IU per liter during treatment (P=0.002). The mean percentage of PNH type III erythrocytes increased from 36.7 percent of the total erythrocyte population to 59.2 percent (P=0.005). The mean and median transfusion rates decreased from 2.1 and 1.8 units per patient per month to 0.6 and 0.0 units per patient per month, respectively (P=0.003 for the comparison of the median rates). Episodes of hemoglobinuria were reduced by 96 percent (P