Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India.
National Institute of Immunohaematology (ICMR), Mumbai, India.
Ann Hematol. 2019 Feb;98(2):289-299. doi: 10.1007/s00277-018-3536-x. Epub 2018 Nov 9.
Thalassaemia are the most common inherited autosomal recessive single gene disorders characterized by chronic hereditary haemolytic anaemia due to the absence or reduced synthesis of one or more of the globin chains. Haemoglobin E-β thalassaemia is the genotype responsible for approximately one half of all severe beta-thalassaemia worldwide. This study proposes to evaluate the effect of various molecular parameters on the response of hydroxyurea. Hydroxyurea was started at an initial dose of 10 mg/kg of body weight/day on 110 transfusion-dependent HbE-β thalassaemia patients. HbF level was measured by HPLC analysis. β-Thalassaemia mutations, XmnI and five other SNPs, and α-globin gene deletions and triplications were detected by ARMS-PCR, RFLP-PCR and Gap-PCR, respectively. Based on the factors for evaluating hydroxyurea-response, 42 patients were responders as they showed an increment of Hb from a mean baseline value of 6.45 g/dl (± 0.70) to 7.78 g/dl (± 0.72) post-therapy. Based on increase in HbF above the median value (14.72%) post-therapy, 78 patients were found to be responders. All the 78 responders showed mean decrease in transfusion of 74.26% (± 8.32) with a maximum decrease of 98.43%. There was a significant correlation between decrease in transfusion and increase in HbF level for all 78 responders. XmnI polymorphism showed the strongest association (p < 0.0001) with increase in HbF levels and Hb levels. Patients with α-globin gene deletions were better responders. It was concluded that hydroxyurea treatment is effective in transfusion-dependent HbE-β thalassaemia patients and the response is best in patients having both XmnI polymorphism and α-deletion.
地中海贫血是最常见的遗传性常染色体隐性单基因疾病，其特征是由于一个或多个珠蛋白链的缺失或合成减少而导致慢性遗传性溶血性贫血。血红蛋白 E-β 地中海贫血是导致全球约一半严重β-地中海贫血的基因型。本研究旨在评估各种分子参数对羟基脲反应的影响。110 名依赖输血的 HbE-β 地中海贫血患者初始剂量为 10mg/kg 体重/天，开始服用羟基脲。通过 HPLC 分析测量 HbF 水平。采用 ARMS-PCR、RFLP-PCR 和 Gap-PCR 分别检测β-地中海贫血突变、XmnI 和其他 5 个 SNP 以及α-珠蛋白基因缺失和三倍体。根据评估羟基脲反应的因素，42 名患者为反应者，因为他们在治疗后 Hb 从平均基线值 6.45g/dl（±0.70）增加到 7.78g/dl（±0.72）。根据治疗后 HbF 值高于中位数（14.72%），发现 78 名患者为反应者。所有 78 名反应者的平均输血减少了 74.26%（±8.32%），最大减少了 98.43%。所有 78 名反应者的输血减少与 HbF 水平升高均呈显著相关。XmnI 多态性与 HbF 水平和 Hb 水平的升高相关性最强（p<0.0001）。α-珠蛋白基因缺失的患者反应更好。结论是羟基脲治疗对依赖输血的 HbE-β 地中海贫血患者有效，并且在同时具有 XmnI 多态性和α-缺失的患者中反应最佳。
