Effect of hydroxyurea on mortality. and morbidity in adult sickle cell anemia - Risks and benefits up to 9 years of treatment
Effect of hydroxyurea on mortality. and morbidity in adult sickle cell anemia - Risks and benefits up to 9 years of treatment
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DOI：
10.1001/jama.289.13.1645
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发表时间：
2003-04-02
影响因子：
120.7
通讯作者：
Terrin, M
中科院分区：
文献类型：
--
作者：
Steinberg, MH;Barton, F;Terrin, M
羟基脲可增加镰状细胞性贫血 (SCA) 患者胎儿血红蛋白 (HbF) 的水平并降低血管闭塞并发症的发病率。高 HbF 水平可降低发病率和死亡率。 目的 确定羟基脲是否能降低 SCA 患者的死亡率。 设计 对最初参与 1992-1995 年进行的羟基脲治疗镰状细胞性贫血 (MSH) 的随机、双盲、安慰剂对照多中心研究的 SCA 患者的死亡率进行长期观察性随访研究，以确定羟基脲是否能减少血管闭塞事件。在 1996 年至 2001 年进行的 MSH 患者随访中，患者可以继续、停止或开始使用羟基脲。在试验期间和随访期间收集数据。 设置美国和加拿大 21 个镰状细胞转诊中心的住院患者和门诊患者。 患者 299 名频繁疼痛发作的成年患者参加了随访。截至 2001 年 5 月，233 名患者的随访数据已完成。 干预 在 MSH 中，患者被随机分配接受羟基脲 (n = 152) 或安慰剂 (n = 147)。 主要结果测量死亡率、HbF 水平、疼痛发作、急性胸部综合征和血细胞计数。该随机试验的目的不是检测死亡率的具体差异。结果 最初的 299 名患者中有 75 名死亡，其中 28% 死于肺部疾病。网织红细胞计数低于 250000/mm(3) 且血红蛋白水平低于 9 g/dL 的患者死亡率增加 (P=.002)。试验完成后，当 HbF 水平低于 0.5 g/dL 时，9 年累积死亡率为 28%，而当 HbF 水平为 0.5 g/dL 或更高时，9 年累积死亡率为 15% (P=.03)。试验期间患有急性胸部综合征的个体死亡率为 32%，而没有急性胸部综合征的个体死亡率为 18% (P=0.02)。试验期间每年疼痛发作 3 次或以上的患者死亡率为 27%，而发作次数较少的患者死亡率为 17% (P=.06)。在这项自我选择治疗的观察性随访中，服用羟基脲与死亡率降低 40% 相关 (P=0.04)。共有 3 例癌症病例，其中 1 例死亡。 结论 因镰状细胞病频繁发作而服用羟基脲的成年患者在 9 年随访后死亡率似乎有所降低。生存率与 HbF 水平和血管闭塞事件的频率有关。是否应该扩大羟基脲治疗的适应症尚不清楚。
Context Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality.Objective To determine whether hydroxyurea attenuates mortality in patients with SCA.Design Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Followup, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period.Setting Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada.Patients Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients.Intervention In the MSH, patients were randomly assigned to receive hydroxyurea (n = 152) or placebo (n = 147).Main Outcome Measures Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts. The randomized trial was not designed to detect specified differences in mortality.Results Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250000/mm(3) and hemoglobin levels lower than 9 g/dL had increased mortality (P=.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/dL after the trial was completed compared with 15% when HbF levels were 0.5 g/dL or higher (P=.03). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P=.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P=.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P=.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal.Conclusions Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown.