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Blood, 1 January 2002, Vol. 99, No. 1, pp. 10-14
PLENARY PAPER
Predictors of fetal hemoglobin response in children with sickle
cell anemia receiving hydroxyurea therapy
Russell E. Ware,
Barry Eggleston,
Rupa Redding-Lallinger,
Winfred C. Wang,
Kim Smith-Whitley,
Charles Daeschner,
Beatrice Gee,
Lori A. Styles,
Ronald W. Helms,
Thomas R. Kinney, and
Kwaku Ohene-Frempong
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.
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.
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