Abstract 5304

Background:

Non-transfused patients with thalassemia intermedia (TI) accumulate iron in their body due to increased gastrointestinal absorption of iron and release of iron from the macrophages. Earlier studies have revealed that serum ferritin does not reflect the severity of iron overload in non-transfused TI patients. The current study aims at evaluating the iron overload status in a group of young hypertransfused TI children.

Materials and Methods:

Eleven patients (mean age 13.18±4.094 years) with TI on regular follow-up at the Pediatric Thalassemia Day Care Centre, Sultan Qaboos University Hospital, Oman were included in the study after approval by the Medical Research and Ethics Committee. All patients had beta gene mutational analysis. They were diagnosed as intermedia because of their definitive TI mutation, late age at presentation (>5 years) and transfusion independence (mean baseline Hb 6.9 g/dl). Patients were treated conventionally with hypertransfusion, and chelation, as guided by their serum ferritin levels. Serum ferritin (2 monthly) was analyzed using the Beckman Coulter Access 2 Immunoassay System.

Based on serum ferritin levels, patients were classified into 2 groups, group 1(six patients) and 2 (five patients) with serum ferritin levels below and above 1000 ng/ml respectively. All patients underwent cardiac T2* MRI assessment. Based on local reference values for T2*MRI, quantification of cardiac iron deposition was categorized as normal, mild, moderate and severe iron overload at values > 20 ms, 14–20 ms, 10–14 ms and < 10 ms respectively. Simultaneous liver iron T2* values were categorized into normal, mild, moderate and severe iron overload at values > 9.1 ms, 7.1–9.0 ms, 3.1– 7.0 ms and <3.0 ms respectively.

Results:

Patients in group 1 and 2 had mean serum ferritin levels of 817.300±244.690 ng/ml and 1983.80±662.862 ng/ml respectively (p = 0.003). Despite this very high variation in serum ferritin values, T2* MRI showed comparable hepatic iron overload status in both the groups with mean hepatic T2* value of 2.51±0.46 ms and 3.4±1.63 ms in group 1 and group 2 respectively. The difference in hepatic T2* between the 2 groups is −0.88 (95% confidence interval −2.44 to 0.68) which is statistically insignificant (p =0.23, t-test). None of the studied patients had myocardial iron deposition (overall mean 36.86±7.8 ms). Other confounders like initial ages at presentation, pre-transfusion hemoglobin levels, durations of transfusion and chelation therapies were statistically insignificant for the 2 groups. No specific pattern of beta gene sequence was noted in either group.

Conclusions:

We conclude in our patients with TI on hypertransfusion, serum ferritin does not reflect their moderate to severe hepatic iron overload status. Inspite of steady serum ferritin trends, evaluation of iron overload by T2* MRI and optimal chelation is strongly recommended in hypertransfused TI patients.

Table 1:

Demographic and laboratory characteristics of the 2 study groups.

Group12
Serum Ferritin, ng/ml <1000 >1000 
Total number of children, n 
Male: Female 2:4 3:2 
Mean age of presentation, years 7.1 7.8 
Mean pre-transfusion hemoglobin, g/dl 7.0 6.8 
Mean duration of transfusion therapy, years 5.0 6.6 
Mean duration of chelation therapy, years 4.3 5.8 
Splenectomy (n) 
Chelation monotherapy (DFP), n (mean dose mg/kg/day) 6 (87) 4 (100) 
Chelation combination (DFP+DFO), n (mean dose mg/kg/day) 1 (100+40) 
Group12
Serum Ferritin, ng/ml <1000 >1000 
Total number of children, n 
Male: Female 2:4 3:2 
Mean age of presentation, years 7.1 7.8 
Mean pre-transfusion hemoglobin, g/dl 7.0 6.8 
Mean duration of transfusion therapy, years 5.0 6.6 
Mean duration of chelation therapy, years 4.3 5.8 
Splenectomy (n) 
Chelation monotherapy (DFP), n (mean dose mg/kg/day) 6 (87) 4 (100) 
Chelation combination (DFP+DFO), n (mean dose mg/kg/day) 1 (100+40) 

n= number of patients DFP=Deferiprone DFO=Desferrioxamine

Table 2.

Serum ferritin levels (ng/ml) T2* MRI values (ms) in the 2 groups

Group 1Group 2
Mean age ± SD, years 12.16 ± 4.91 14.4 ± 2.88 
Median age, range 12.5 (4-18) 15 (10-18) 
Mean serum ferritin ± SD, ng/ml 817.300 ± 244.690 1983.80 ± 662.862 
Median serum ferritin, range 903.5 (323-990) 1898 (1330-3008) 
Mean hepatic T2* ± SD, ms 2.51 ± 0.46 3.4 ± 1.63 
Median hepatic T2*, range 2.35 (2.1-3.1) 3.3 (1.4-5.6) 
Mean cardiac T2* ± SD, ms 37.41 ± 10.08 36.2 ± 4.92 
Mean cardiac T2*, range 33.9 (29-55) 36 (30.3-42.6) 
Group 1Group 2
Mean age ± SD, years 12.16 ± 4.91 14.4 ± 2.88 
Median age, range 12.5 (4-18) 15 (10-18) 
Mean serum ferritin ± SD, ng/ml 817.300 ± 244.690 1983.80 ± 662.862 
Median serum ferritin, range 903.5 (323-990) 1898 (1330-3008) 
Mean hepatic T2* ± SD, ms 2.51 ± 0.46 3.4 ± 1.63 
Median hepatic T2*, range 2.35 (2.1-3.1) 3.3 (1.4-5.6) 
Mean cardiac T2* ± SD, ms 37.41 ± 10.08 36.2 ± 4.92 
Mean cardiac T2*, range 33.9 (29-55) 36 (30.3-42.6) 
Figure 1.

Comparison of serum ferritin levels (ng/ml) T2* MRI values (ms) in the 2 groups.

Figure 1.

Comparison of serum ferritin levels (ng/ml) T2* MRI values (ms) in the 2 groups.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.