Safety and efficacy of dose-escalation hydroxyurea therapy in very young children with sickle cell anemia: A retrospective cohort study

Objective The BABY HUG trial of hydroxyurea in very young children with sickle cell anemia (SCA) established the safety and clinical benefit of hydroxyurea therapy at a fixed dose in this age group but did not assess the safety and efficacy of escalation to maximum tolerated dose (MTD) in this age group. Methods To address this question, we conducted a retrospective chart review of children with HbSS or HbS beta(0)Thalassemia started on hydroxyurea therapy before the age of two years between 2011 and 2018 at the Texas Children's Hematology Center. Results We identified 102 patients ranging from 5 to 24 months in age initiated on hydroxyurea therapy during the study period. MTD was achieved in 86 patients, of whom 51 were still at MTD at the end of monitoring. Overall laboratory response to hydroxyurea was superior in our cohort to that seen in the BABY HUG treatment arm, but MTD declined with age of initiation of treatment. There was a trend toward fewer clinical adverse events in our cohort with maintenance of MTD. Conclusions Dose escalation to MTD appears to be safe in very young children with SCA and results in significant and sustained increases in hemoglobin concentration and HbF. Our findings also suggest that conventional dose-escalation to MTD may be challenging in children under the age of two years due to the relatively low neutrophil counts commonly seen in this age group.