Page 174 - 2021_09-Haematologica-web

P. Kountouris et al.
Table 2. Demographic and clinical features of the cohort of patients.
Alive N=443 (%)
214 (77.0) 229 (88.4)
186 (73.5) 257 (90.5)
43.1 (8.1)
99 (81.8) 115 (82.1) 186 (81.2) 43 (91.5)
77 (90.6) 293 (86.9) 70 (77.8) 2 (8.3)
XmnI polymorphism
CC 407 (88.3) 54 (11.7) 461 CT 19(100) 0(0) 19
Died Total N=94 (%) N=537
64 (23.0) 278 30 (11.6) 259
67 (26.5) 253 27 (9.5) 284
30.4 (11.0)
22 (18.2) 121 25 (17.9) 140 43 (18.8) 229 4 (8.5) 47
8 (9.4) 85 44 (13.1) 337 20 (22.2) 90 22 (91.7) 24
Comparison of proportion alive and died (P)
χ2 = 11.4, 1 d.f., P<0.001 χ2 = 25.5, 1 d.f., P<0.001
χ2 = 2.9, 3 d.f., P=0.401
χ2 = 6.8, 2 d.f., P=0.0341
χ2 = 1.8, 5 d.f., P=0.8781
Sex Male
Female
Year of birth < 1974
≥ 1974
Age, at end of study period
or death (years, mean, SD)
Clinic Larnaca Limassol Nicosia Paphos
HBB genotypeb Severe Moderate Mild
Not known
α-globin gene number 1
2
3
4
5 2(100) 0(0) 2 6 1(100) 0(0) 1 Not known 12 (27.3) 32 (72.7) 44
2 (100) 14 (93.3) 84 (89.4) 328 (86.5)
0 (0) 2 1 (6.7) 15 10 (10.6) 94 51 (13.5) 379
Not known
Splenectomy
Childhood
Adulthood or not splenectomised Not known
Iron chelation therapy
DFO only
DFO switched to DFP-containing DFO switched to DFX
17 (29.8)
108 (74.5) 334 (91.0) 1 (4.2)
52 (42.6) 311 (93.7) 80 (96.4)
χ2 = 1.5, 1 d.f., P=0.2251 145 χ2 = 22.7, 1 d.f., P<0.001a
40 (70.2) 57
37 (25.5)
33 (9.0) 367
24 (95.8) 25
70 (57.4)
21 (6.3) 332
χ2 = 176, 2 d.f., P<0.001
122 3 (3.6) 83
aAnalysis restricted to the population in which the variable was known.bOne patient was removed from the genotype analysis because thalassemia was caused by α-locus dupli- cations co-inherited with β-thalassemia trait.23 d.f.: degrees of freedom; SD: standard deviation; DFO: deferoxamine; DFP: deferiprone; DFX: deferasirox.
time periods of follow-up. There was a lower incidence of overall mortality in the period 1980-89, but no significant differences in mortality rates in subsequent time periods and no overall trend. There was a significant decrease in cardiac mortality over the last three time periods, and an increased incidence of deaths due to liver disease, cancer and infections during successive decades. However, there were insufficient numbers of deaths from these causes in each individual decade for a statistical analysis. The propor- tion of deaths due to heart disease was lower in those with a mild genotype (6 out of 20, 30%) than in those with mod- erate (23 out of 44, 52%) and severe (4 out of 8, 50%) geno- types. These differences did not reach statistical signifi- cance. Of the 15 subjects who died due to infectious causes, six of nine with known splenectomy status had been splenectomized. Five of 94 (5.3%) patients who died were HCV RNA positive at the time of death. Three of these died of heart failure and two from liver disease. HCV infection could be a contributing factor for these deaths, but was like- ly to be the primary cause in only two (2.1%) cases.
Survival analysis
We constructed two models to explore risk factors associated with mortality. In both models, data were right-censored on September 30, 2018, at death or bone marrow transplantation. In the first model, we considered the entire follow-up period and evaluated non-modifiable risk factors. These comprised sex, year of birth, treatment clinic and genotype. To assess the impact of treatment factors (iron chelation therapy and splenectomy), a sec- ond model was constructed. This took into account the licensing of the oral iron chelator deferiprone in 1999 and general availability for prescription from 2000. Deferiprone was sometimes used as single therapy and frequently in combination with deferoxamine, depending on the clinician’s assessment of iron overload severity. A second oral chelator, deferasirox was licensed and avail- able for prescription in 2006 and there was switching between different chelator regimes over time after 2006 to optimize therapy for each individual. Since it would be biased to compare chelator efficacy during the period
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