Hydroxyurea for children with sickle cell anemia in sub-Saharan Africa
| Autor: | Tshilolo, L, Tomlinson, G, Williams, TN, Santos, B, Olupot-Olupot, P, Lane, A, Aygun, B, Stuber, SE, Latham, TS, McGann, PT, Ware, RE, For the REACH investigators |
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| Přispěvatelé: | Wellcome Trust |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Pediatrics
medicine.medical_specialty YOUNG-CHILDREN Sub saharan HYDROXYCARBAMIDE TRANSFUSIONS Anemia MULTICENTER Pain REACH Investigators Anemia Sickle Cell 030204 cardiovascular system & hematology Body weight Article DISEASE Hydroxycarbamide 03 medical and health sciences 0302 clinical medicine Medicine General & Internal MALARIA Antisickling Agents General & Internal Medicine medicine Humans Hydroxyurea 030212 general & internal medicine Child Africa South of the Sahara 11 Medical and Health Sciences Science & Technology Dose-Response Relationship Drug business.industry MORTALITY Infant Neglected Diseases General Medicine Retention rate medicine.disease Sickle cell anemia Malnutrition DOPPLER FLOW VELOCITIES Child Preschool SURVIVAL TRIAL business Life Sciences & Biomedicine Malaria medicine.drug |
| ISSN: | 0196-6731 |
| Popis: | BACKGROUND: Hydroxyurea 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. METHODS: We 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). RESULTS: A 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). CONCLUSIONS: Hydroxyurea 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. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731.) |
| Databáze: | OpenAIRE |
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