title: Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy.
abstract: 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 =.001), baseline hemoglobin concentration (P =.01), MTD dose (P =.02), and compliance (P =.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 =.05) and baseline WBC count (P =.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.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. ware005@mc.duke.edu
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: Barry
authors.initials: B
authors.lastname: Eggleston
authors.forename: Rupa
authors.initials: R
authors.lastname: Redding-Lallinger
authors.forename: Winfred C
authors.initials: WC
authors.lastname: Wang
authors.forename: Kim
authors.initials: K
authors.lastname: Smith-Whitley
authors.forename: Charles
authors.initials: C
authors.lastname: Daeschner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gee
authors.forename: Lori A
authors.initials: LA
authors.lastname: Styles
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Helms
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kinney
authors.forename: Kwaku
authors.initials: K
authors.lastname: Ohene-Frempong
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy*; D000986:Antisickling Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D005319:Fetal Hemoglobin / Q000032:analysis*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D020714:Maximum Tolerated Dose; D010349:Patient Compliance; D010976:Platelet Count; D017701:Reticulocyte Count; D016896:Treatment Outcome
chemical_list: D000986:Antisickling Agents; D006454:Hemoglobins; D005319:Fetal Hemoglobin; D006918:Hydroxyurea