Adding hydroxyurea to chronic transfusion therapy for sickle cell anemia reduces transfusion burden

Transfusion. 2024 Nov 24. doi: 10.1111/trf.18073. Online ahead of print.

Abstract

Background: Chronic red blood cell (RBC) transfusion is an established therapy to prevent stroke in patients with sickle cell anemia (SCA). It is unclear if adding daily hydroxyurea treatment to chronic transfusion is beneficial.

Study design and methods: We conducted a phase 2 clinical trial (NCT03644953) investigating the addition of dose-escalated hydroxyurea to chronic transfusion for patients with SCA receiving simple chronic transfusion for stroke prevention. Simple chronic transfusion therapy was administered as per the same protocol before and after hydroxyurea treatment in which the volume transfused was dependent on the pretransfusion hemoglobin (Hb).

Results: A total of 14 participants enrolled with nine completing one year of combination hydroxyurea and transfusion (HAT) therapy after reaching hydroxyurea target dose. No participant who discontinued the study prematurely had a serious adverse event attributed to HAT. Among the nine participants who completed the study, eight participants achieved a reduction in RBC transfusion volume with a median reduction of -19.4 mL/kg/year (interquartile range -31.8, -2.8 mL/kg/year), p = .02, when comparing pre- and post-HAT time periods. With the addition of hydroxyurea participants had a significant increase in pretransfusion Hb S% but this was balanced by an increased Hb F% and decreased lactate dehydrogenase. One participant developed a pretransfusion Hb >11 g/dL and Hb S > 45% that required holding hydroxyurea and changing to partial manual exchange transfusions. No patient had evidence of cerebrovascular disease progression.

Discussion: Hydroxyurea added to chronic transfusion therapy for patients with SCA is feasible and decreases RBC transfusion volume requirements.

Keywords: blood conservation; chronic transfusion; hydroxyurea; sickle cell disease; stroke prevention.