Abstract
Sickle cell/ß-Thalassemia is a common disease in areas where ß-Thal and ßS genes are endemic, like in Sicily. In the current study we evaluated clinical and hematological data of Sicilian patients with Sickle cell/ß-Thalassemia treated with Hydroxyurea (HU). The endpoint of the study was to evaluate the efficacy of HU in terms of reduction of sickle cell crises after 2 years of treatment in comparison with the 2 years before. Moreover, we evaluated the outcome after long-term treatment. Fortytwo patients (18 males, mean age 36, range 18–53) were treated with HU (mean dosage 15 mg/kg, range 10–30) for an average 6.6 years follow-up (range 3–9 years). Twentytwo were ß0/ßS and 20 ß+/ßS genotype. All had 3 or more crises in the year before starting HU. We observed a significant reduction in sickle cell crises (7.8 ± 6.9 crises per year versus 0.9 ± 1.8 per year, P < 0.0001), hospitalizations (2.5 ± 2.9 per year versus 0.3 ± 1.5, P < 0.0001), and days in hospital (22.4 ± 21.9 per year versus 1.2 ± 2.3, P < 0.0001). Altogether, there was a 86% reduction in vasoocclusive events in comparison with the 2 years before (P < 0.001). Moreover, there was a significant increase of MCV (71.4 versus 97.5fl, P < 0.0001), HbF (7.5 versus 25.2 %, P < 0.0001), and decrease of WBC (11.4 versus 9.2 109/L P < 0.01) and reticulocytes (14.1 versus 10.2%, P< 0.01). Finally, redution of hyperdense cells and increase of erithropoyetin were seen. After a mean follow-up of 6.6 years, 39 patients are alive. Three died (2 end stage HCV related liver disesases, 1 bleeding after ERCP). Nine of the 40 alive patients developed complications: 1 acute chest syndrome, 2 strokes, 2 myocardial infarctions, 4 bone necrosis. Brain MRI of 15 patients after and during a mean of 6.9 years of HU treatment showed 2 new onset strokes, 1 of which in a patient with a previous stroke. Moreover, 4 patients developed new onset asymptomatic ischemic brain lesions. In every case there had been a significant reduction of sickle cell crises. There were two cases of cancer, occurring in two patients who were brother and sister: lung cancer in the former, a proeviously heavy smoker, breast cancer in the latter. No further serious adverse events were seen. Five patients with iron overload were treated with Deferiprone: no drug interaction with HU was noticed. Our study confirms that HU is effective in reducing clinical relevant crises of patients with Sickle cell/ß-Thalassemia. However, our preliminary data suggest that chronic organ damages are not prevented by HU. Safety has to be assessed by more prolonged studies.
Red cells in sickle cell crisis: observations on the pathophysiology of crisis