is it time to revisit classification of thalassemia ... - 1st... · epidemiology of thalassaemia in...
TRANSCRIPT
1st International Working Group on Thalassemia:
IS IT TIME TO REVISIT CLASSIFICATION
OF THALASSEMIA SYNDROMES ?
CAMPUS OF HEMATOLOGY
"Franco e Piera Cutino"
A.O.R. "Villa Sofia - V. Cervello"
Palermo (Italy)
September 15-16, 2017
Dr. Soteroula Christou
Nicosia Thalassaemia Center
Arch. Makarios III Hospital
CYPRUS
Epidemiology of Thalassaemia in Cyprus
• 1:7 (15%) Cypriots are -thalassaemia carriers
• 1:49 (2%) couples at risk for -thalassaemia major (both partners heterozygous)
• 1:58 (1.7%) newborns annually expected to be homozygous (60-70 babies)
• 1:1000 (0.1%) prevalence of homozygotes in the population
• 1:5 (20%) carry -thalassaemia genes
• 1:500 (0.2%) carry sickle cell gene
Cyprus Thalassaemia patients’ population
Cyprus Thalassaemia patients’ population
β-Thalassaemia Major Intermediate Total
535 119 654
H-Disease 419
Sickel Cell
Dyndromes49
Hereditary
Spherocytosis13
Transplanted 27
Total 1162
Nicosia Thalassemia Clinic Patients’ Population
Nicosia Thalassaemia Clinic
β-Thalassaemia Major Intermediate
Ex.
Intermedia
te
Total
223 34 23 280
H-Disease 253
Sickel Cell Dyndromes 28
Hereditary Spherocytosis 11
Transplanted 8
Total 580
Thalassaemia Major Patients' Age Distribution
0
5
10
15
20
25
Age 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66
Thalassaemia Intermediate Patients' Age Distribution
0
0,5
1
1,5
2
2,5
3
3,5
Age 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78
Number
Number
New births of Thalassaemia Patients
0
10
20
30
40
50
60
YEAR
1915
1920
1924
1932
1936
1940
1943
1946
1949
1952
1955
1958
1961
1964
1967
1970
1973
1976
1979
1982
1985
1988
1991
1994
1997
2000
2003
2006
2009
2012
2015
Ex Thalassaemia Intermediate Patients
• Total: 23
-Male :12
-Female:11
• Age 53 (33-74)
- Male Age:49 (33-72)
- Female Age:57 (41-74)
Ex Thalassaemia Intermediate Patients' Age Distribution
0
0,5
1
1,5
2
2,5
3
3,5Age 33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
Number
Reasons for starting regular Blood Transfusion
Pulm. HypertensionTotal Male Female
6 3 3
% 26 25 27
FatigueTotal Male Female
6 3 3% 26 25 27
Extramedulary
Haematopoetic
Masses
Total Male Female
10 5 5
% 44 42 45
PriapismTotal Male Female
1 1 0% 4 8 0
Chelation Treatment in Cyprus
Clinic
Number of Patients
DFO DFO+DF DFEXJAD
ETotal
Nicosia 47 149 20 43 259
Limassol 28 77 39 27 171
Larnaca 19 79 16 22 136
Paphos 8 24 13 7 52
Total 102 329 88 99 618
Clinic DFO% DFO+DF% DF%EXJADE
%Total
Nicosia 18,2 57,52% 7,70% 16,60% 100%
Limassol 16,30% 45,00% 22,80% 15,70% 100%
Larnaca 13,97% 58,00% 11,70% 16,10% 100%
Paphos 15% 46% 25% 14% 100%
Total 18,10% 52,10% 17,90% 11,80% 100%
Effectiveness of chelators according to
Ferritin levels (statistical analysis)
Ferritin statistics
DFX DF DFX+DF EXJADE
Sample 1 2 3 4
obs (n) 54 24 128 42
mean (μ) 2653 919 1831 2058
Standard deviation (s) 3536 971 1887 2206
Comparison of means for Ferritin
DF < DFX+DF DFX+DF < EXJADE EXJADE < DFX DF < DFX
Null hypothesis H0: μ2=μ3 H0: μ3=μ4 H0: μ4=μ1 H0: μ2=μ1
Alternative hypothesis H1: μ2<μ3 H1: μ3<μ4 H1: μ4<μ1 H1: μ2<μ1
Standard error 259.05 378.99 589.40 520.45
Degrees of freedom 23.00 41.00 41.00 23.00
Test statistic -3.52 -0.60 -1.01 -3.33
P-value 0.0009 0.2759 0.1591 0.0014
Not reject the null
hypothesis?Rejected Not rejected Marginally not rejected Rejected
Effectiveness of chelators according to Ferritinlevels
• Conclusions (Preliminary data)
-Deferiprone is the most effective in
removal iron
- Deferiprone plus Desferrioxamine ,
Exjade are the second effective chelator
-Desferrioxamine is the less effective
chelator
Effectiveness of chelators according to Heart T2* (statistical analysis)
T2* Heart statistics
DFX DF DFX+DF EXJADE
Sample 1 2 3 4
obs (n) 40 24 101 23
mean (μ) 26 29 28 29
Standard deviation
(s)7 7 8 5
Comparison of means for T2* Heart
DF > EXJADEEXJADE >
DFX+DFDFX+DF > DFX DF > DFX
Null hypothesis H0: μ2=μ4 H0: μ4=μ3 H0: μ3=μ1 H0: μ2=μ1
Alternative hypothesis H1: μ2>μ4 H1: μ4>μ3 H1: μ3>μ1 H1: μ2>μ1
Standard error 1.79 1.24 1.40 1.91
Degrees of freedom 22 22 39 23
Test statistic -0.02 0.52 1.58 1.48
P-value 0.5081 0.3032 0.0616 0.0768
Not reject the null
hypothesis?Not rejected Not rejected Rejected Rejected
Effectiveness of chelators according to Heart T2*
• Conclusions (Preliminary data)
- Deferiprone, Deferiprone plus
Desferrioxamine , Exjade have the same
effect in removing iron for the heart
- Desferrioxamine is less effective in
removing iron from the heart
Effectiveness of chelators according to Liver T2* (statistical analysis)
T2* Liver statistics
DFX DF DFX+DF EXJADE
Sample 1 2 3 4
obs (n) 40 24 101 23
mean (μ) 11 13 12 12
Standard deviation
(s)8 10 9 7
Comparison of means for T2* Liver
DF > EXJADEEXJADE >
DFX+DFDFX+DF > DFX DF < DFX
Null hypothesis H0: μ2=μ4 H0: μ4=μ3 H0: μ3=μ1 H0: μ2=μ1
Alternative hypothesis H1: μ2>μ4 H1: μ4>μ3 H1: μ3>μ1 H1: μ2>μ1
Standard error 2.50 1.75 1.57 2.37
Degrees of freedom 22 22 39 23
Test statistic 0.22 0.17 0.55 0.72
P-value 0.4153 0.4329 0.2934 0.2406
Not reject the null
hypothesis?Not rejected Not rejected Not rejected Not rejected
Effectiveness of chelators according to Liver T2*
• Conclusions (Preliminary data)
- Deferiprone, Deferiprone plus
Desferrioxamine , Exjade and
Fesferrioxamine have the same effect in
removing iron from the liver
Main complications in Thalassaemics in Cyprus(all patients=647)
No of patients (m/f) % of patients
Hypothyroidism84 (37/47) 13.0
Hypoparathyroidism8 (6/2) 1.2
Hypogonadism184 (88/96) 28.4
Diabetes95 (51/44) 14.7
Heart failure/arrhythmias57 (38/19) 8.8
Osteoporosis218 (119/99) 33.7
Chronic hepatitis C18 (10/6) 2.8
Chronic hepatitis B5 (4/1) 0.8
Cirrhosis10 (8/2) 1.5
Thrombosis 38 5.9
Pregnancies of women with thalassaemiain Cyprus
ClinicNumber of
Women
Number of
Pregnancies
Number of
born
Children
Twins Triplets
Nicosia 96 151 167 14 0
Limassol 31 48 53 3 1
Larnaca 38 55 68 5 1
Pafos 12 20 21 1 0
Total 175 272 307 23 2
Cyprus thalassaemics: Overall Survival
Survival Functions
Years
403020100
Cu
m S
urv
iva
l
1.0
.9
.8
.7
Birth Cohort
1980-
1980- censored
1975-9
1975-9 censored
1970-5
1970-5 censored
1965-9
1965-9 censored
1965-9 n=104
1970-4 n=192
1975-9 n=184
1980- n=92
Logrank 7.4
p=0.06
Cyprus thalassaemics: Thalassaemia-related mortality
Survival Functions
Years
403020100
Cu
m S
urv
iva
l
1.0
.9
.8
.7
Birth Cohort
1980-
1980- censored
1975-9
1975-9 censored
1970-5
1970-5 censored
1965-9
1965-9 censored
1965-9 n=104
1970-4 n=192
1975-9 n=184
1980- n=92
Logrank 13.3
P=0.004
Cyprus thalassaemics 1965-cohort: Overall survival
Overall Survival
Years
403020100
Cum
Surv
ival
1. 00
.90
.80
.70
Survival Function
Censored
N=572
Events 60
Cyprus thalassaemics 1965- cohort: Thalassaemia related survival
Thal-related survival
Years
403020100
Cum
Surv
ival
1. 00
.90
.80
.70
Survival Function
Censored
N=572
Events:47
Annual deaths in Cyprus
0
1
2
3
4
5
6
7
8
9
10
1975 1980 1985 1990 1995 2000 2005 2010
Year
Nu
mb
er
Cardiac
All
