Daar S, Pathare A V
Day Care Unit, Department of Haematology, College of Medicine, Sultan Qaboos University, Muscat, 123, Sultanate of Oman.
Ann Hematol. 2006 May;85(5):315-9. doi: 10.1007/s00277-005-0075-z. Epub 2006 Feb 1.
Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L(1)) since 1987 is useful but showed poor efficacy when used alone as compared to DFX. We therefore decided to compare DFX alone with a prospective combined therapy with DFX and L(1) in beta thalassemia major patients with iron overload. We studied 91 patients with beta thalassemia major (mean age+/-SD, 15.02+/-5.8; range 2-30 years) attending the day care unit for regular transfusional support. They received packed red cells every 3-4 weeks to maintain pretransfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40 mg kg(-1) day(-1) by subcutaneous infusion for 8-10 h on 4-5 nights each week for the past several years. However, due to various reasons, they had developed considerable transfusional iron overload. These patients were allocated to prospectively receive additional therapy with oral iron chelator L(1) at 75 mg kg(-1) day(-1) body weight in three divided doses with food after informed consent and continued to receive treatment with DFX as per the above dosage. Of the 91 patients, six developed severe gastrointestinal (GI) upset, two agranulocytosis, two arthropathy, one persistently raised liver enzymes, two died owing to sepsis, and two received allogeneic bone marrow transplantation. Amongst the remaining 76 patients, 21 were found noncompliant (not taking DFX regularly, but taking L(1) regularly). Thus, in the 55 evaluable patients {6-48 months on combination therapy; mean [(+/-SD)22+/-12 months]}, the mean serum ferritin (+/-SD) fell dramatically from 3,088 (+/-1,299) ng/ml (DFX alone) to 2,051 (+/-935) ng/ml (DFX and L(1); p<0.001). It is interesting to note that there was also a significant improvement in the myocardial function as assessed by the ejection fraction (p<0.004) and fractional shortening (p<0.05) in those patients (n=42) who could be studied after being on combination therapy for a minimum of 1 year. The study emphasizes that beta thalassemia major patients with transfusional iron overload can be successfully treated with a combination of DFX and L(1). Our results also demonstrate a significant statistical improvement after as little as 6 months of combination therapy. Furthermore, these improvements lead to a progressive fall in the mean serum ferritin. Lastly, the study also demonstrates significant improvement in the echocardiographic parameters of myocardial performance in these patients receiving combination therapy.
铁过载是重型β地中海贫血（TM）患者发病和死亡的主要原因，尤其是心力衰竭导致的死亡。因此，成功的铁螯合治疗对于TM的最佳管理至关重要。尽管去铁胺（DFX）一直是治疗输血性铁过载的主要铁螯合剂，但依从性是实现最佳治疗效果的主要障碍。自1987年以来可用的口服铁螯合剂去铁酮（L(1)）很有用，但与DFX相比，单独使用时疗效不佳。因此，我们决定比较单独使用DFX与DFX和L(1)联合治疗对重型β地中海贫血铁过载患者的效果。我们研究了91例重型β地中海贫血患者（平均年龄±标准差，15.02±5.8岁；范围2 - 30岁），他们在日间护理病房接受定期输血支持。他们每3 - 4周接受一次浓缩红细胞输注，以维持输血前血红蛋白浓度高于9 g/dl。在过去几年中，他们每周4 - 5个晚上通过皮下输注接受每日剂量为40 mg/kg的DFX，持续8 - 10小时。然而，由于各种原因，他们出现了相当严重的输血性铁过载。在获得知情同意后，这些患者被前瞻性地分配接受口服铁螯合剂L(1)，剂量为75 mg/kg体重，分三次与食物同服，并继续按上述剂量接受DFX治疗。91例患者中，6例出现严重胃肠道不适，2例出现粒细胞缺乏症，2例出现关节病，1例肝酶持续升高，2例因败血症死亡，2例接受了异基因骨髓移植。在其余76例患者中，发现21例不依从（未定期服用DFX，但定期服用L(1)）。因此，在55例可评估患者中（联合治疗6 - 48个月；平均[(±标准差)22±12个月]），平均血清铁蛋白（±标准差）从单独使用DFX时的3,088（±1,299）ng/ml显著降至（DFX和L(1)联合治疗时的）2,051（±935）ng/ml（p<0.001）。有趣的是，在接受联合治疗至少1年后可进行研究的患者（n = 42）中，通过射血分数（p<0.004）和缩短分数（p<0.05）评估的心肌功能也有显著改善。该研究强调，重型β地中海贫血输血性铁过载患者可通过DFX和L(1)联合治疗成功治愈。我们的结果还表明，联合治疗仅6个月后就有显著的统计学改善。此外，这些改善导致平均血清铁蛋白逐渐下降。最后，该研究还表明，接受联合治疗的这些患者的心肌性能超声心动图参数有显著改善。
