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Blood, 1 August 2007, Vol. 110, No. 3, pp. 1043-1047.
Prepublished online as a Blood First Edition Paper on April 11, 2007; DOI 10.1182/blood-2006-11-057893.
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Submitted November 27, 2006
Accepted March 27, 2007
Hydroxyurea therapy lowers transcranial doppler flow
velocities in children with sickle cell anemia
Sherri A Zimmerman, William H Schultz, Shelly Burgett, Nicole A Mortier, and Russell E. Ware*
Division of Pediatric Hematology/Oncology, and Duke Pediatric Sickle Cell Program, Duke University Medical Center, Durham, NC, United States
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, United States
* Corresponding author; email: russell.ware{at}stjude.org.
Hydroxyurea has hematological and clinical efficacy in SCA, but its effects on transcranial doppler (TCD) flow velocities remain undefined. Fifty-nine children initiating hydroxyurea therapy for clinical severity had pre-treatment baseline TCD measurements; 37 with increased flow velocities ( 140 cm/sec) were then enrolled in an IRB-approved prospective Phase II trial with TCD velocities measured at maximum tolerated dose (MTD) and one year later. At hydroxyurea MTD (mean ± 1SD = 27.9 ±2.7 mg/kg/day), significant decreases were observed in the right MCA (166 ±27 cm/sec to 135 ±27 cm/sec, p<.001) and left MCA velocities (168 ±26 cm/sec to 142 ±27 cm/sec, p<.001). The magnitude of TCD velocity decline was significantly correlated with the maximal baseline TCD value. At hydroxyurea MTD, 14 of 15 children with conditional baseline TCD values improved, while 5 of 6 with abnormal TCD velocities whose families refused transfusions became <200 cm/sec. TCD changes were sustained at follow-up. These prospective data indicate that hydroxyurea can significantly decrease elevated TCD flow velocities, often into the normal range. A multicenter trial is warranted to determine the efficacy of hydroxyurea for the management of increased TCD values, and ultimately for primary stroke prevention in children with SCA.
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