The Experimental And Clinical Research Of Iron Metabolism In Patients With Myelodysplastic Syndrome

ObjectiveTo detect the incidence of the C282Y and H63D mutations in patients with myelodysplastic syndrome(MDS) and aplastic anemia(AA),and analyze the relationship between the HFE mutations and iron metabolism parameters,evaluation indices of organ function injury at iron overload.MethodsThe incidence of the C282Y and H63D mutations in 271 MDS,402 AA patients enrolled between October 2004 and April 2008 were measured by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) combining with DNA sequencing,and iron metabolism parameters and clinical characteristics were retrospectively analyzed.ResultsNo C282Y mutations and compound heterozygote were observed in the entire cohort.The genotype distribution of H63D heterozygous and homozygous did not differ significantly in AA cases from those in controls(9.7%vs.10.2%,0.25%vs.0.24% respectively,Pearson Chi-square p both＞0.05).While the frequency of the H63D heterozygous in MDS patients is significantly lower than controls(4.1%vs.10.7%, Pearson Chi-square p=0.002).H63D homozygous was not found in MDS patients.In both MDS and AA patients without RBC transfusion history,Serum ferritin(SF) and transferrin saturation values(TS) values were significantly higher,serum iron concentration(SI) values were close to or higher than normal,and unsaturated iron-binding capacity(UIBC) values were significantly lower.Comparing the pretransfusion SF,SI,UIBC,TIBC and TS values between HFE-positive and HFE-wildtype MDS groups,no significant difference was found(all P＞0.05%); However,SI values were significantly higher in the HFE-positive AA cases than those in HFE-negative ones[42.6(24.6-60.4)umol/Lvs.32.0(8.4-63.3 )umol/L,P=0.011].Besides, no association between HFE gene mutations and the other iron metabolism parameters was found in AA patients.There is no significantly difference in Alanine amino transferase(ALT),Aspartate amino transferase(AST),fasting blood sugar(FBS),the percentage of patients with abnormal electrocardiogram(ECG),Hb,WBC,absolute neutrophil count(ANC),PLT,mean corpuscular volume(MCV),and mean corpuscular hemoglobin(MCH) between HFE-positive and HFE-wildtype MDS and AA groups irrespective of the red blood cell transfusion history(all P＞0.05%).Conclusion1.The results suggest that the distribution of C282Y and H63D mutations has ethnic and genetic difference,the frequency in Chinese population is lower than that of Caucasian. MDS and AA patients have the instinct of iron overload。2.the mutations of HFE gene are not main factors of iron overload in Chinese patients with myelodysplastic syndrome and aplastic anemia. ObjectiveTo evaluate iron metabolism in patients with myelodysplastic syndrome(MDS) and analyse the impact of iron overload on prognosis of patients with MDS.MethodsIron metabolism parameters and clinical characteristics of 206 MDS patients between 1990 and 2007 were retrospectively studied.Survival data were evaluated by applying Kaplain-Maier.ResultsSerum ferritin(SF) level was significantly higher in both the total MDS patients [360.3(3-2800.5)ug/L]and those without RBC transfusion before diagnosis[328 (3-1644.5)ug/L].No relationship between SF level and disease course was found in patients without RBC transfusion before diagnosis;and SF level of low-risk MDS patients(RA,RARS,RCMD,RCMD-RS,5q-) was higher than high-risk patients (RAEB-1,RAEB-2)[423.76(3.0-1644.5)ug/L vs 286.4(26.8-1014.3)ug/L, P=0.002].The level of Alanine amino transferase(ALT),Aspartate amino transferase (AST),Gamma-glutamyl transpeptidase(GGT) were significantly higher,while reticulocytes count(Ret) was obviously lower in patients with SF≥500ug/L than those with SF＜500ug/L(all P＜0.05);and the percentage of patients with abnormal electrocardiogram(ECG) or echocardiogram was higher in patients with SF≥500ug/L than those with SF＜500ug/L.There was no correlation between SF≥500ug/L at diagnosis and poor prognosis.ConclusionAnemia results in increased duodenal iron absorption in MDS patients and develops iron overload,meanwhile RBC transfusion can accelerate accumulation of iron in vivo.SF level≥500ug/L can lead to dysfunction of important organs such as liver, heart and bone marrow.SF≥500ug/L can be considered as the threshold to initiate iron-chelation treatment. ObjectiveTo study primarily the effect of iron chelation treatment(ICT) on myelodysplastic syndrome patients with iron overload and the adverse effect.MethodClinical characteristics and peripheral parameters of Seven MDS patients were retrospectively analyzed before and during and after ICT.ResultThe mean serum ferritin(SF) level was(1521.84±812.1)μg/L at the start of ICT, and decreased to(829.4±945.9)μtg/L at the end of ICT.However,there was no significant difference in SF values between before and after ICT(P=0.183).The serum iron concentration(SI),total iron-binding capacity(TIBC),and transferrin saturation values(TS) of three patients decreased,while unsaturated iron-binding capacity(UIBC) values increased after ICT.Hb improvement and/or transfusion requirement decrease were found in four patients during or after ICT,two of whom had a significant concomitant increase in platelet(PLT) counts(P values both＜0.05) or prolonged PLT transfusion interval.The mean corpuscular volume(MCV) values of one patient were lower significantly after ICT compared to that before ICT(P=0.009). The increased Hb values or PLT counts were accompanied by reduction in SF values. The obvious improvement of hemopoiesis was seen after at least 2 weeks of iron chelation.The fast blood sugar(FBS) level in one patient decreased after ICT,and at the same time,SF values also decreased.ConclusionEffective ICT could improve bone marrow hemopoiesis during short term,and ameliorate life of quality in MDS patients.ICT should be recommended as one of routine therapy in MDS patients with iron overload secondary to transfusion dependency.