Hematologic Effects of Hydroxyurea Treatment in Children with Hb SC and SB+ Thalassemia

Background: The effects of hydroxyurea in clinically severe hemoglobin SC (Hb SC) and hemoglobin Sβ+ thalassemia patients (Hb Sβ+) are not well defined. The largest previous report reviewed 15 children with Hb SC treated with hydroxyurea (Yates, et al: Pediatr Blood Cancer 2013;60: 323-325). Prior studies describe a mixed hematologic pattern of response, but all pediatric reports show an increase in fetal hemoglobin and MCV in Hb SC. To further evaluate the hematologic effect of hydroxyurea in these compound heterozygous conditions, we reviewed 27 patients with Hb SC and 7 with Hb Sβ+ treated to date at our institution

Methods: The medical records of all children treated at least a year with hydroxyurea for clinically severe Hb SC and Hb Sβ+ were reviewed. Age at start and indication for hydroxyurea were documented. Laboratory values were recorded at hydroxyurea start and at the visit that fell closest to one year of therapy. Data collected included hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), white blood cell count (WBC), absolute neutrophil count (ANC), platelet count (PLT), absolute reticulocyte count (ARC), hemoglobin F % (Hb F), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and total bilirubin. The milligram/kilogram dose of hydroxyurea was recorded at start and at 12 months of treatment. Paired differences were compared at baseline and 12 months of treatment.

Results: The average age at hydroxyurea start for patients with Hb SC was 9.4 years + 3.8. Fifteen of the 27 patients were male. Hb Sβ+ patients’ average age at start was 10.7 years + 6.9. Five of the 7 Hb Sβ+ patients were male. Twenty-six of the 27 patients with Hb SC were treated with hydroxyurea for recurrent painful crises and one Hb SC patient started hydroxyurea for recurrent acute chest syndrome. All 7 Hb Sβ+ patients were treated with hydroxyurea due to recurrent painful crises. The average dose of hydroxyurea for Hb SC patients was 22 mg/kg/day and 21mg/kg/day for the Hb Sβ+ group. There was no significant change in mg/kg dose from hydroxyurea start to the 12 month interval. For patients with Hb SC, significant decreases were seen in the following lab values with p values noted in parenthesis: WBC (0.0001), PLT (0.0122), ARC (0.0002) , ANC (0.0002) and AST(0.0408). Significant increases were seen in MCV (0.0003) and Hb F (0.0181). However, Hb F and MCV values in Hb SC patients (average Hb F of 7.4% (+5.8%) and MCV of 87 fl (+14) after 12 months of treatment) were not as high as seen in good hydroxyurea responders with Hb SS disease Hb, Hct and bilirubin did not significantly change in patients with Hb SC. For Hb Sβ+, statistically significant decreases were seen in WBC (0.0157), PLT (0.0476), and ANC (0.0047). MCV also increased in Hb SB+ from 70 fl (+6.63) at baseline to 80 fl (+5.4) at 12 months (p= 0.0054). Hb F did not change in HbSβ+ patients with values of 7% (+ 4.2) at baseline and 9.5% (+ 5) at 12 months (p= 0.4042). Similar to the Hb SC group, Hb and Hct did not significantly increase in the Hb Sβ+ patients.

Conclusions: This report of the largest pediatric cohort of Hb SC and Hb Sβ+ patients treated with hydroxyrea to date shows hematologic effect, although with some differences from typical response in patients with Hb SS disease. Most notably, Hb and Hct did not change in either group which is important given concerns about viscosity increase in patients with higher baseline values. Further study in larger numbers of patients is needed to evaluate hematologic effect and clinical outcome.