MDS患者祛铁治疗与缓解EPO抵抗的初步研究

Iron Chelation Therapy and Its Influence on the Alleviation of EPO Resistance in MDS Patients

本研究旨在探讨骨髓增生异常综合征(MDS)患者袪铁治疗后红细胞生成素(EPO)、血红蛋白(Hb)、重组EPO(rEPO)的变化及EPO与血清铁蛋白(SF)的相关性。检测172例MDS患者及30例健康对照者SF、EPO浓度、血清铁(SI)、总铁结合力(TIBC)、C反应蛋白(CRP)、Hb;根据CRP值对SF进行调整。对34例低危组、SF>1 000 mg/L的患者给予袪铁胺治疗,比较治疗前后SF、EPO、SI、TIBC、Hb的变化。对58例低危组、EPO<1 000 U/L的患者给予rEPO治疗,比较铁过载组与非铁过载组袪铁治疗前后EPO抵抗的发生率。结果表明:非铁过载组EPO浓度高于正常对照组(997.44±473.48 vs 467.27±238.49)(P<0.05);铁过载组EPO浓度高于无铁过载组及正常对照组(3257.59±697.19 vs 997.44±473.48;3257.59±697.19 vs 467.27±238.49)(P均<0.05);铁过载组EPO抵抗发生率高于非铁过载组(18/35 vs 2/23)(P=0.001),铁过载组MDS患者EPO与SF呈显著正相关(r=0.310)(P=0.036)。袪铁治疗后SF、SI、TIBC及EPO浓度均较治疗前明显下降(3942.38±641.82 vs 2266.35±367.31;48.61±10.65 vs 28.52±12.61;59.84±12.62 vs 33.76±15.43;3808.01±750.22 vs 1954.78±473.18)(P均<0.05),Hb升高(35±18 vs 57±21)(P=0.046),部分EPO抵抗患者恢复疗效。结论:袪铁治疗能增强贫血MDS患者对EPO反应,缓解EPO抵抗,降低EPO病理性升高,提升Hb水平,减少输血依赖。

This study was aimed to investigate the changes of erythropoietin （EPO）, hemoglobin （Hb） and recombinant EPO （rEPO） levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin（SF）. A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron （SI）, total iron binding capacity （TIBC）, C-reaction protein （CRP） and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low- risk （SF 〉 1 000 mg/L） receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO 〈 1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group （ 997.44 ± 473.48 vs 467.27 ± 238.49, P 〈 0.05 ）. Obviously, the level of EPO in iron overload group was higher than that in non-iron overload group and control group （ 3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002）. Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group （ 18/35 vs 2/23, P =0. 001 ）, and the level of EPO and SF was positively related to each other in iron overload group （r =0. 310,P =0.036）. After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy （3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028 ;48.61± 10.65 vs 28.52±12.61, P = 0. 034 ;59.84 ± 12.62 vs 33.76± 15.43, P = 0. 045 ;3808.01±750.22 vs 1954.78 ± 473.18, P = 0.042）. Moreover, the level of Hb increased（35 ± 18 vs 57 ±21, P =0.046） and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviale EPO resistance in patients wtih anemic MDS, decrease the pathological level of EPO, enhance Hb levels and reduce the dependency on blood transfusion.