Safety and Efficacy of Prolonged Hydroxycarbamide Administration in Patients with Sickle Cell Disease in Northwestern Greece

Abstract

Hydroxycarbamide (HC) is a ribonucleotide reductase inhibitor which promotes fetal hemoglobin (HbF) induction and has proven efficacy in sickle cell disease (SCD) patients. Given its mechanism of action and prior reports of genotoxicity in animal models, concern exists regarding long-term safety in relation to its cytotoxic effects. The purpose of this study was to retrospectively analyze the long-term (range 3-20 years, median 11) HC-derived clinical and biological effects, in 30 SCD patients (age range 20-68 years) from one referral center. HC treatment resulted in significant reduction of painful crises and transfusions, increase of HbF and hemoglobin as well as drop of white blood cell count and lactate dehydrogenase values. During the long term follow up time the following disease complications were observed: pulmonary hypertension (2 patients), leg ulcers (1 patient) and renal impairment (1 patient). Seven patients discontinued HC therapy because of scheduled pregnancy (3), severe neutropenia (2) and non-compliance (2). One poor HC compliant patient died of pulmonary embolism. No case of malignancy was observed. This retrospective study of most prolonged administration of HC, provides data supporting the safety and the well-established usefulness of chronic administration of HC in SCD.