Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980-2004.

BACKGROUND AND OBJECTIVES: A large number of patients with thalassemia major have been born and treated exclusively in Cyprus. They have been managed according to standard international practice, but few have been transplanted. In 1999, a combination chelation regime with desferrioxamine and deferiprone was introduced. We analyzed survival trends in Cypriots and tried to identify factors associated with prolonged survival. DESIGN AND METHODS: We had incomplete information on births pre-1974 and complete information from 1974 onwards. Clinical data were incomplete pre-1980 and complete thereafter. We analyzed data on 539 patients born after 1960 and followed over the period 1980 to the end of 2004. RESULTS: There were 58 deaths, 31 (53.4%) of which where due to cardiac causes. In the complete birth cohort of 284 patients born after 1974, survival (95% CI) at 10, 20 and 30 years was 100% (0); 98.5% (96.1-99.4) and 92.7% (86.7-96.1) respectively. There was a significant trend of increasing cardiac deaths between 1980 and 2000 (p<0.001) and a decline after 2000 (p=0.06). In multivariate survival analysis, protective effects were found for female sex (hazard ratio, 0.37, 95% CI 0.21-0.66; p<0.001), and post-2000 follow-up (hazard ratio, 0.44, 95% CI 0.20-0.99; p<0.05), but not for genotype, treatment center or birth cohort. INTERPRETATION AND CONCLUSIONS: Most patients born after 1974 survive to at least the age of 30. There has been a marked improvement in survival for patients of all ages since 2000, which may be due to the introduction of combination chelation therapy.

The impact of iron overload and genotype on gonadal function in women with thalassaemia major.

OBJECTIVE: The purpose of this study is to evaluate the impact of chronic iron overload and genotype on gonadal function in women with thalassaemia major. PATIENTS AND METHODS: The study population consists of 101 women aged 15-48 years who were treated between 1981 and 1999. These women were divided into two groups according to their genotype: [A=no modifying genetic factor and B=presence of modifying factors], and into four groups according to their menstrual history: NM (normal menstruation), OLM (oligomenorrhea), PA (primary amenorrhea), and SA (secondary amenorrhea). RESULTS: Women with NM maintained eumenorrhoea for 14.62 years, whereas those with SA did so for 6.94 years. The serial values of both FSH and LH after stimulation with GnRH were lower in women with SA and PA (p<0.05) compared to women with OLM and NM. The average value of the minimum, mean and maximum ferritin levels over a period of 20 years displayed an increasing trend from women with NM to those with SA and PA. The lower levels of ferritin in women in Group A did not protect them from developing SA. In addition women with SA, who belong to Group A, had a shorter duration of eumenorrhoea compared to the ones with SA who belong to Group B. CONCLUSIONS: Although the pathogenesis of gonadal dysfunction in thalassaemia is known to be the consequence of iron overload, this study demonstrates that genotype acts as an independent variable, contributing to the development of SA in thalassaemic women.