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From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia
Despite documented laboratory and clinical benefits of hydroxyurea for children with sickle cell anemia (SCA), the drug's long-term safety and efficacy remains poorly defined. The HUSOFT trial and extension study examined feasibility, toxicity, and hematological efficacy of hydroxyurea in infan...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603125/ https://www.ncbi.nlm.nih.gov/pubmed/25526439 http://dx.doi.org/10.1097/MD.0000000000000215 |
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author | Hankins, Jane S. Aygun, Banu Nottage, Kerri Thornburg, Courtney Smeltzer, Matthew P. Ware, Russell E. Wang, Winfred C. |
author_facet | Hankins, Jane S. Aygun, Banu Nottage, Kerri Thornburg, Courtney Smeltzer, Matthew P. Ware, Russell E. Wang, Winfred C. |
author_sort | Hankins, Jane S. |
collection | PubMed |
description | Despite documented laboratory and clinical benefits of hydroxyurea for children with sickle cell anemia (SCA), the drug's long-term safety and efficacy remains poorly defined. The HUSOFT trial and extension study examined feasibility, toxicity, and hematological efficacy of hydroxyurea in infants with SCA. This report describes HUSOFT participants who have continued hydroxyurea therapy for 15 years. With IRB approval, medical records were reviewed for clinical, laboratory, and growth parameters. Twenty-eight infants enrolled in the original 2-year HUSOFT study received open-label liquid hydroxyurea at 20 mg/kg/day; 17 completed the extension study with dose escalation to 30 mg/kg/day. Eight of these 17 (6 girls and 2 boys, all HbSS) have continued on daily hydroxyurea for at least 15 years (median age at last follow-up 17.6 years) without interruption. All hematologic indices (Hb concentration, mean corpuscular volume (MCV), fetal hemoglobin) showed sustained effect after 15 years. The median maximum tolerated dose of hydroxyurea has decreased from 30 to 26 mg/kg/day (range 19.5–31.2); neutropenia [absolute neutrophil count (ANC) < 1.0 × 10(9)/L] prompting temporary drug discontinuation occurred a total of 10 times in 4 subjects and there was no severe neutropenia (ANC < 0.5 × 10(9)/L). Growth rates over 15 years continued at the 50th percentile for both height and weight, and puberty occurred without delay (age range 10–14 years). There were 5.1 vaso-occlusive events (pain and acute chest syndrome)/100 patient years, 7.3 packed red blood cell transfusions/100 patient years. No malignancies, strokes, or deaths occurred. At last follow up, all subjects were at appropriate grade level (10–12 grade) with no history of repeated grades. A cohort of young teenagers with SCA who initiated treatment in infancy have had sustained and continued hematological benefits for a decade and a half. Growth and sexual development are normal and comparable to the general pediatric population. Continuous hydroxyurea therapy since infancy appears safe and efficacious in SCA. |
format | Online Article Text |
id | pubmed-4603125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-46031252015-10-27 From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia Hankins, Jane S. Aygun, Banu Nottage, Kerri Thornburg, Courtney Smeltzer, Matthew P. Ware, Russell E. Wang, Winfred C. Medicine (Baltimore) 4800 Despite documented laboratory and clinical benefits of hydroxyurea for children with sickle cell anemia (SCA), the drug's long-term safety and efficacy remains poorly defined. The HUSOFT trial and extension study examined feasibility, toxicity, and hematological efficacy of hydroxyurea in infants with SCA. This report describes HUSOFT participants who have continued hydroxyurea therapy for 15 years. With IRB approval, medical records were reviewed for clinical, laboratory, and growth parameters. Twenty-eight infants enrolled in the original 2-year HUSOFT study received open-label liquid hydroxyurea at 20 mg/kg/day; 17 completed the extension study with dose escalation to 30 mg/kg/day. Eight of these 17 (6 girls and 2 boys, all HbSS) have continued on daily hydroxyurea for at least 15 years (median age at last follow-up 17.6 years) without interruption. All hematologic indices (Hb concentration, mean corpuscular volume (MCV), fetal hemoglobin) showed sustained effect after 15 years. The median maximum tolerated dose of hydroxyurea has decreased from 30 to 26 mg/kg/day (range 19.5–31.2); neutropenia [absolute neutrophil count (ANC) < 1.0 × 10(9)/L] prompting temporary drug discontinuation occurred a total of 10 times in 4 subjects and there was no severe neutropenia (ANC < 0.5 × 10(9)/L). Growth rates over 15 years continued at the 50th percentile for both height and weight, and puberty occurred without delay (age range 10–14 years). There were 5.1 vaso-occlusive events (pain and acute chest syndrome)/100 patient years, 7.3 packed red blood cell transfusions/100 patient years. No malignancies, strokes, or deaths occurred. At last follow up, all subjects were at appropriate grade level (10–12 grade) with no history of repeated grades. A cohort of young teenagers with SCA who initiated treatment in infancy have had sustained and continued hematological benefits for a decade and a half. Growth and sexual development are normal and comparable to the general pediatric population. Continuous hydroxyurea therapy since infancy appears safe and efficacious in SCA. Wolters Kluwer Health 2014-12-02 /pmc/articles/PMC4603125/ /pubmed/25526439 http://dx.doi.org/10.1097/MD.0000000000000215 Text en © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the Creative Commons Attribution-NonCommercial License, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc/4.0 |
spellingShingle | 4800 Hankins, Jane S. Aygun, Banu Nottage, Kerri Thornburg, Courtney Smeltzer, Matthew P. Ware, Russell E. Wang, Winfred C. From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title | From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title_full | From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title_fullStr | From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title_full_unstemmed | From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title_short | From Infancy to Adolescence: Fifteen Years of Continuous Treatment With Hydroxyurea in Sickle Cell Anemia |
title_sort | from infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia |
topic | 4800 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603125/ https://www.ncbi.nlm.nih.gov/pubmed/25526439 http://dx.doi.org/10.1097/MD.0000000000000215 |
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