The hemoglobin F (HbF) promoting agent hydroxyurea (HU) has been established as an effective therapy for adults with sickle cell disease (SCD) who develop frequent pain episodes, acute chest syndrome, severe vaso-occlusive events, or severe symptomatic anemia. However, concerns have been raised for long-term safety issues of HU in relation to its cytotoxic effects, which are attributed to ribonucleotide reductase inhibition. We analyzed the clinical effects of chronic use of HU in adult SCD patients treated in a referral Academic center.

Medical files of 29 adult patients (10 male, median age 42 years, range 29–68 years) followed at our Thalassemia Unit for the last 17 years were retrieved, and detailed data were recorded and analyzed. Four patients had homozygous SCD and 25, sickle cell/beta thalassemia.

The median follow up time was 10 years (range 3–17 years), the total follow-up time was 289 patient-years and the total HU exposure period was 308 patient-years. The mean dose of HU administered was 29.3 mg/kg/day. The main clinical outcomes of HU therapy are shown in Table 1. In terms of efficacy, HU induced marked increase of HbF and substantial reduction of painful crises and transfusions needed, all outcomes designated statistically significant. HU therapy was also associated with significant increase of hemoglobin (Hb) levels, as well as with reduction of serum lactate dehydrogenase levels (LDH) and white blood cell count (WBC). In terms of toxicity, one poor HU compliant female patient died of pulmonary embolism. Disease complications observed during the long follow up time were: pulmonary hypertension in 2 patients, leg ulcers in one patient and renal impairment in one patient. Seven patients discontinued HU therapy (mean treatment duration 8.4 years) because of scheduled pregnancy (3 patients), severe neutropenia (2 patients) and non-compliance (2 patients). No patient developed cancer.

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This retrospective study, which analyzed data of most prolonged administration of HU, provides data supporting the efficacy and safety of chronic administration of HU in SCD adults.

No relevant conflicts of interest to declare.