{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:36:30Z","timestamp":1778214990882,"version":"3.51.4"},"reference-count":22,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:p>In the phase I\/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF). To identify predictors of the HbF response to hydroxyurea therapy, baseline clinical and laboratory values (age, sex, hemoglobin concentration, %HbF, reticulocytes, white blood cell [WBC], platelets, and serum chemistries), as well as treatment variables (number of toxicities, noncompliance, MTD dose, and MTD blood counts) were analyzed in 53 HUG-KIDS children who achieved MTD. Baseline %HbF values (P\u2009=\u2009.001), baseline hemoglobin concentration (P\u2009=\u2009.01), MTD dose (P\u2009=\u2009.02), and compliance (P\u2009=\u2009.02) were significantly associated with a higher %HbF at MTD; in contrast, age, sex, number of toxicities, and other baseline hematologic parameters were not. After adjusting for variations in baseline %HbF, the baseline reticulocyte count (P\u2009=\u2009.05) and baseline WBC count (P\u2009=\u2009.05) were also significantly associated with a higher %HbF at MTD. Hydroxyurea-induced increases in the hemoglobin concentration and mean corpuscular volume (both higher absolute values at MTD and larger positive changes from baseline values), as well as hydroxyurea-induced decreases in reticulocytes and WBC count, were significantly associated with a higher %HbF at MTD. These data suggest that selected baseline laboratory parameters, a higher MTD dose with attention to compliance, and greater therapy-related changes in blood counts may predict the HbF response to hydroxyurea therapy for children with sickle cell anemia. The HbF response to hydroxyurea is variable and complex, however, and even children with low baseline %HbF values can develop substantial increases in %HbF at MTD.<\/jats:p>","DOI":"10.1182\/blood.v99.1.10","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"10-14","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":130,"title":["Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy"],"prefix":"10.1182","volume":"99","author":[{"given":"Russell E.","family":"Ware","sequence":"first","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Eggleston","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupa","family":"Redding-Lallinger","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winfred C.","family":"Wang","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Smith-Whitley","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Daeschner","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Gee","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori A.","family":"Styles","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald W.","family":"Helms","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Kinney","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwaku","family":"Ohene-Frempong","sequence":"additional","affiliation":[{"name":"From Duke University Medical Center, Durham, NC; Children's Hospital of Boston, MA; Children's Hospital of Philadelphia, PA; Oakland Children's Hospital, CA; East Carolina University, Greenville, NC; St Jude Children's Research Hospital, Memphis, TN; the University of North Carolina at Chapel Hill, and Rho Federal Systems Division, Inc, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021217103752800_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3101(24)00238-X","article-title":"Fetal hemoglobin, sickling, and sickle cell disease.","volume":"37","author":"Charache","year":"1990","journal-title":"Adv Pediatr."},{"key":"2020021217103752800_B2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM199107043250103","article-title":"Pain in sickle cell disease: rates and risk factors.","volume":"325","author":"Platt","year":"1991","journal-title":"N Engl J Med."},{"key":"2020021217103752800_B3","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/ajmg.1320270305","article-title":"The relationship between fetal hemoglobin and disease severity in children with sickle cell anemia.","volume":"27","author":"Odenheimer","year":"1987","journal-title":"Am J Med Genet."},{"key":"2020021217103752800_B4","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1542\/peds.84.3.500","article-title":"Mortality in children and adolescents with sickle cell disease.","volume":"84","author":"Leikin","year":"1989","journal-title":"Pediatrics."},{"key":"2020021217103752800_B5","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease: life expectancy and risk factors for early death.","volume":"330","author":"Platt","year":"1994","journal-title":"N Engl J Med."},{"key":"2020021217103752800_B6","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1056\/NEJM199008093230602","article-title":"Treatment of sickle cell anemia with hydroxyurea and erythropoietin.","volume":"323","author":"Goldberg","year":"1990","journal-title":"N Engl J Med."},{"key":"2020021217103752800_B7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1056\/NEJM199301143280202","article-title":"A short-term trial of butyrate to stimulate fetal-globin-gene expression in the \u03b2-globin disorders.","volume":"328","author":"Perrine","year":"1993","journal-title":"N Engl J Med."},{"key":"2020021217103752800_B8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1182\/blood.V84.1.339.339","article-title":"Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate.","volume":"84","author":"Dover","year":"1994","journal-title":"Blood."},{"key":"2020021217103752800_B9","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1182\/blood.V79.10.2555.2555","article-title":"Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia.","volume":"79","author":"Charache","year":"1992","journal-title":"Blood."},{"key":"2020021217103752800_B10","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJM199505183322001","article-title":"Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia.","volume":"332","author":"Charache","year":"1995","journal-title":"N Engl J Med."},{"key":"2020021217103752800_B11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0022-3476(96)70121-X","article-title":"Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia.","volume":"129","author":"Jayabose","year":"1996","journal-title":"J Pediatr."},{"key":"2020021217103752800_B12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0022-3476(96)70335-9","article-title":"Hydroxyurea therapy in children severely affected with sickle cell disease.","volume":"128","author":"Scott","year":"1996","journal-title":"J Pediatr."},{"key":"2020021217103752800_B13","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1182\/blood.V88.6.1960.bloodjournal8861960","article-title":"Hydroxyurea for the treatment of severe sickle cell anemia: a pediatric clinical trial.","volume":"88","author":"Ferster","year":"1996","journal-title":"Blood."},{"key":"2020021217103752800_B14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/00043426-199707000-00009","article-title":"Three year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. 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