Abstract
BACKGROUND: Treatment-associated fetal hemoglobin (HbF) expression patterns in children with sickle cell disease (SCD) have not been fully described. The objective of this study was to compare HbF expression profiles (HbF and F-cells) in the peripheral blood of pediatric SCD patients receiving hydroxyurea (HU), chronic transfusions (Tx) or no chronic therapy (Ctrl). PROCEDURE: Peripheral blood samples were collected from SCD patients between 1 month and 21 years of age and immunostained with anti-HbF and anti-HbA antibodies. Erythrocytes containing HbF (F-cells) were enumerated with this dual staining method. HbF was measured using chromatography (HPLC). RESULTS: Blood from 44 Ctrl patients ≤ 4 years of age was compared with that from older children (50 Ctrl, 17 HU, 17 Tx). Among the older children, the percentage of both HbF and F-cells in the Tx group was significantly decreased compared to the control (HbF 5.4 ± 4.2% vs. 11.0 ± 7.2%, P = 0.003; F-cells 30.2 ± 16.3% vs. 43.8 ± 20.4%, P = 0.0071). While the distribution of F-cells was significantly increased in the HU group (56.3 ± 17.1% vs. 43.8 ± 20.4%, P = 0.016), the increase in HbF was less robust (14.7 ± 6.4% vs. 11.0 ± 7.2%, P = 0.051). Positive correlations of HbF and F-cell distributions were noted in all groups (P < 0.0001 for all groups). In serial samples from individual patients, relatively static patterns of HbF and F-cell distribution were noted. CONCLUSION: Pediatric SCD patients possess distinct patterns of HbF switching and silencing in peripheral blood erythrocytes. Thereafter, erythrocyte HbF expression level and distribution are maintained with both patient- and treatment-specific patterns that may be useful for predicting the need or response to HbF-modulating therapy.