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可溶性白细胞介素2受体比值作为毛细胞白血病反应的早期标志物以及白细胞介素28B基因型与α干扰素治疗的预后相关性

sIL2R ratio as early marker for response in hairy cell leukemia and the prognostic relevance of IL28B genotype to interferon-α therapy.

作者信息

Jud Stéphanie, Goede Jeroen S, Senn Oliver, Spanaus Katharina, Manz Markus G, Benz Rudolf

机构信息

Departement of Hematology, University Hospital Zurich, Zurich, Switzerland.

University of Zurich, Zurich, Switzerland.

出版信息

Ann Hematol. 2017 May;96(5):757-763. doi: 10.1007/s00277-017-2943-8. Epub 2017 Feb 18.

Abstract

Interferon-α (IFNα) was the first effective drug therapy for hairy cell leukemia (HCL). Nowadays, it is used as an alternative treatment in selected patients. Due to unlimited treatment time, monitoring and early prediction of response are important. Moreover, IFNα is used in the therapy of chronic hepatitis C, where a single nucleotide polymorphism of interleukin-28B gene (IL28B) correlates with therapy response. The role of this polymorphism in therapy response of IFNα-treated patients with HCL is unknown. Thirty-seven HCL patients treated between 1978 and 2014 were included in this study. Treatment strategy and response parameters (blood cell counts, soluble interleukin-2 receptor (sIL2R), and bone marrow examination) have been assessed. Relative decrease of sIL2R was correlated with outcome parameters. Response parameters of IFNα-treated patients were correlated with IL28B polymorphism. Twenty-one patients were analyzed for the correlation of sIL2R ratio and outcome. After 1 and 3 months of therapy (IFNα or cladribine (CDA)), the median sIL2R level showed a relative decrease of 79 and 91%. These decreases significantly correlate with time to complete remission (CR, p = 0.029 and p = 0.018). Correlation analyses of IL28B genotype with outcome parameters are not significant. Six patients (16%) were diagnosed with secondary malignancies, and one death was registered (median follow-up time 14 years). IFNα is a safe, effective, and well-tolerated long-term treatment in HCL. Relative decreases of sIL2R levels correlate with time to CR and are useful as early predictor for response. There is no significant correlation between IL28B polymorphism and treatment response to IFNα. Graphical abstract.

摘要

干扰素-α(IFNα)是毛细胞白血病(HCL)的首个有效药物治疗方法。如今,它在特定患者中用作替代治疗。由于治疗时间无限制,监测和早期反应预测很重要。此外,IFNα用于慢性丙型肝炎的治疗,其中白细胞介素-28B基因(IL28B)的单核苷酸多态性与治疗反应相关。这种多态性在IFNα治疗的HCL患者治疗反应中的作用尚不清楚。本研究纳入了1978年至2014年间接受治疗的37例HCL患者。评估了治疗策略和反应参数(血细胞计数、可溶性白细胞介素-2受体(sIL2R)和骨髓检查)。sIL2R的相对降低与结局参数相关。IFNα治疗患者的反应参数与IL28B多态性相关。分析了21例患者sIL2R比值与结局的相关性。治疗1个月和3个月后(IFNα或克拉屈滨(CDA)),sIL2R水平中位数相对降低了79%和91%。这些降低与完全缓解时间显著相关(CR,p = 0.029和p = 0.018)。IL28B基因型与结局参数的相关性分析不显著。6例患者(16%)被诊断为继发性恶性肿瘤,记录到1例死亡(中位随访时间14年)。IFNα是HCL中一种安全、有效且耐受性良好的长期治疗方法。sIL2R水平的相对降低与CR时间相关,可作为反应的早期预测指标。IL28B多态性与IFNα治疗反应之间无显著相关性。图形摘要。

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