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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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RED CELLS
Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anemia
Sherri A. Zimmerman1,
William H. Schultz2,
Shelly Burgett1,
Nicole A. Mortier2, and
Russell E. Ware2
1 Duke Pediatric Sickle Cell Program and Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC;
2 Department of Hematology, St Jude Children's Research Hospital, Memphis, TN
Hydroxyurea has hematologic and clinical efficacy in sickle cell anemia (SCA), but its effects on transcranial Doppler (TCD) flow velocities remain undefined. Fifty-nine children initiating hydroxyurea therapy for clinical severity had pretreatment baseline TCD measurements; 37 with increased flow velocities ( 140 cm/s) were then enrolled in an institutional review board (IRB)–approved prospective phase 2 trial with TCD velocities measured at maximum tolerated dose (MTD) and one year later. At hydroxyurea MTD (mean ± 1 SD = 27.9 ± 2.7 mg/kg per day), significant decreases were observed in the right middle cerebral artery (MCA) (166 ± 27 cm/s to 135 ± 27 cm/s, P < .001) and left (MCA) (168 ± 26 cm/s to 142 ± 27 cm/s, P < .001) velocities. 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 less than 200 cm/s. 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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