Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa
Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa
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DOI：
10.1056/nejmoa1813598
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发表时间：
2019-01-10
影响因子：
158.5
通讯作者：
McElhinney, Kathryn
中科院分区：
文献类型：
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作者：
Tshilolo, Leon;Tomlinson, George;McElhinney, Kathryn
背景：羟基脲是治疗镰状细胞性贫血的有效方法，但在负担最重的撒哈拉以南非洲地区进行的研究很少。共存的条件，如营养不良和疟疾可能会影响的可行性，安全性，和优势的hydroxyurea在低资源setting.METHODSWe招收儿童1至10岁的镰状细胞贫血在四个撒哈拉以南非洲国家。儿童接受了6个月的羟基脲治疗，剂量为每天每公斤体重15至20毫克，随后剂量递增。终点评估可行性（入组、保留和依从性）、安全性（剂量水平、毒性效应和疟疾）和益处（实验室变量、镰状细胞相关事件、输血和存活率）。606名儿童完成了筛查，并开始接受平均（+/- SD）剂量为17.5 +/- 1.8 mg/kg/天的羟基脲治疗。治疗3年时的留存率为94.2%。羟基脲治疗导致血红蛋白和胎儿血红蛋白水平显著升高。5.1%的受试者发生了与实验室变量相关的剂量限制性毒性事件，低于方案规定的安全性阈值。在治疗期间，每100患者年发生20.6起剂量限制性毒性反应，而治疗前每100患者年发生20.7起事件。与治疗前相比，使用羟基脲后临床不良事件的发生率降低，包括血管闭塞性疼痛的发生率（98.3 vs. 44.6起事件/100患者-年;发生率比，0.45; 95%置信区间[CI]，0.37 - 0.56），非疟疾感染（142.5 vs. 90.0起事件/100患者-年;发生率比，0.62; 95% CI，0.53 - 0.72），疟疾（46.9 vs. 22.9起事件/100患者-年;发生率比，0.49; 95% CI，0.37 - 0.66），输血（43.3 vs. 14.2起事件/100患者-年;发生率比，0.33; 95% CI，0.23 - 0.47）和死亡（3.6 vs. 1.1例死亡/100患者-年;发病率比，0.30; 95%CI，0.10 ~ 0.88）.CONCLUSIONSHydroxyurea治疗生活在撒哈拉以南非洲的镰状细胞性贫血儿童是可行和安全的。使用羟基脲降低了血管闭塞事件、感染、疟疾、输血和死亡的发生率，这支持了更广泛获得治疗的需求。
BACKGROUNDHydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings.METHODSWe enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell-related events, transfusions, and survival).RESULTSA total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (+/- SD) dose of 17.5 +/- 1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88).CONCLUSIONSHydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment.