RESUMEN
In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of deferoxamine, suggesting that this drug is an alternative option in cases in which deferoxamine and deferasirox are contraindicated.
Asunto(s)
Deferoxamina/administración & dosificación , Quelantes del Hierro/administración & dosificación , Sobrecarga de Hierro/terapia , Piridonas/administración & dosificación , Talasemia beta/terapia , Adulto , Agranulocitosis/inducido químicamente , Agranulocitosis/fisiopatología , Artralgia/inducido químicamente , Artralgia/fisiopatología , Terapia por Quelación/métodos , Deferiprona , Deferoxamina/efectos adversos , Femenino , Ferritinas/metabolismo , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/mortalidad , Modelos Lineales , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/fisiopatología , Piridonas/efectos adversos , Análisis de Supervivencia , Reacción a la Transfusión , Talasemia beta/metabolismo , Talasemia beta/mortalidad , Talasemia beta/patologíaRESUMEN
We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by alpha-hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by alpha-hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by alpha-hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilli in vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.