Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.
Name: Deferasirox
Description: Deferasirox tablets ( 250 mg or 500 mg) dispersed in a drinkable solution, 10 mg/kg/day, once daily for 12 monthsType: DrugDeferasirox HC
Name: Venesection
Description: Treated with venesection every 8-10 day for 12 months, or until serum-ferritin has been reduced to about 50 µg/L.Type: OtherVenesection HC
Name: Deferasirox
Description: Deferasirox tablets ( 250 mg or 500 mg) dispersed in a drinkable solution starting with 10 mg/kg/day, once daily for 2 weeks and thereafter 20 mg/kg/day for 11,5 months.Type: DrugDeferasirox MDS
Description: Marker of oxidative DNA damage
Measure: Change of 8-oxodG in urine Time: 0, 6 and 12 monthsDescription: Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme
Measure: Change of Cu,Zn-SOD activity in erythrocyte hemolysate Time: 0, 6 and 12 monthsDescription: Serum analysis
Measure: Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin. Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatmentDescription: Morning spot urine sample.
Measure: Urine routine test strip for detection of blood, protein, and nitrite Time: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 monthsAllocation: Randomized
Parallel Assignment
There are 3 SNPs
Inclusion Criteria: - Patients with hemochromatosis, aged > 30 years, C282Y- homozygote, with serum-ferritin =/> 1000 µg/L - Patients aged > 18 years with verified low-risk or intermediate-1 risk of myelodysplastic syndrome, with normal cytogenetics and serum-ferritin > 1500 µg/L, or with a transfusion history of =/> red- blood-cell-transfusions. Exclusion Criteria: - Previous or current venesection - MDS patients eligible for hematopoietic stem cell transplantation - Subject complies with one or more of the following standard exclusion criteria for MRI examination; - If the patient has a pacemaker. --- C282Y ---
The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y ---
Homozygosity for C282Y is the strongest risk factor for serious iron overload and disease which develops after a long-lasting, asymptomatic period. --- C282Y ---
The study by Phatak et al (2010) was the first clinical trial to demonstrate the safety and efficacy of deferasirox in patients with C282Y-homzygot hemochromatosis. --- C282Y ---
In Norway the prevalence of C283Y homozygosity is approximately 0.75 in both genders. --- C283Y ---
The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y --- --- H63D ---