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HBB genotype in TDT in Cyprus
Figure 3. Boxplots illustrating the distribution of transfusion data among groups with HBB genotypes of different severity. Statistically significant associations, deter- mined with the Wilcoxon rank-sum non-parametric test, are shown.
standard guidelines was forward-estimated at 63% by the age of 50 years. This was based on a review of available data in which clinical follow-up was only reported up to 30 years of age. The estimate of 80.4% in this study is more robust and significantly more optimistic. Life expectancy in the general population of Cyprus has been reported recent- ly using national statistics over the period 1986–2012.25 About 90–95% are expected to survive to 50 years, and our data would suggest that a diagnosis of thalassemia reduces the percentage surviving to this age by about 15%. These data should be helpful in discussing outcomes of tha- lassemia with new parents, in refining health economic models, comparing outcomes of new therapies with stan- dard care, and in making treatment decisions about use of alternative donor transplantation, where overall survival with unrelated, or mismatched family donors are currently less than 80%.26
Causes of death appear to be changing with longer term follow-up of TDT patients. We have confirmed reduction in deaths due to cardiac causes over the past 20 years, as reported previously in this cohort1 and in other studies.5 We also noted increasing mortality related to liver disease and
infection in this cohort, a finding that has also been report- ed in recent registry studies from Sicily and Greece.6,27 The increasing numbers of deaths due to malignancies has also been noted previously.28 Although the incidence of cancer naturally increases with age, and it has not been established that the incidence is significantly different from that in the general population, the types of malignancy appear to be different, notably with a higher representation of hepato- cellular carcinoma. Further follow-up of the cohort and evaluation in other similar studies will be needed to con- firm this finding.
The distribution of HBB genotypes in this study is consis- tent with the known distribution of thalassemia alleles in the Cypriot population.29,30 There is a predominance of homozygosity for IVS I-110 G>A, a severe β+ variant caus- ing a cryptic splice site in the first intron of HBB which reduces functional β-globin mRNA to about 20% of nor- mal.31 Next in prevalence is IVS 1-6 T>C, causing aberrant splicing at the first intronic junction of HBB, with a less severe reduction in β-globin mRNA. Being a milder variant, it has been classified as β++ or β+ in different studies. We have selected the former annotation for this study.21 The
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