title: sIL2R ratio as early marker for response in hairy cell leukemia and the prognostic relevance of IL28B genotype to interferon-α therapy.
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.
authors.affiliation: Departement of Hematology, University Hospital Zurich, Zurich, Switzerland. stephanie.jud@uzh.ch.|University of Zurich, Zurich, Switzerland. stephanie.jud@uzh.ch.
authors.forename: Stéphanie
authors.identifier: http://orcid.org/0000-0001-5235-0473
authors.initials: S
authors.lastname: Jud
authors.affiliation: Departement of Hematology, University Hospital Zurich, Zurich, Switzerland.|University of Zurich, Zurich, Switzerland.|Kantonsspital Winterthur, Winterthur, Switzerland.
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Goede
authors.affiliation: University of Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Senn
authors.affiliation: Departement of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Spanaus
authors.affiliation: Departement of Hematology, University Hospital Zurich, Zurich, Switzerland.|University of Zurich, Zurich, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
authors.affiliation: Departement of Hematology, Kantonsspital Münsterlingen, Münsterlingen, Switzerland.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Benz
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007943:Leukemia, Hairy Cell / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012008:Recurrence; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D015415:Biomarkers; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D015375:Receptors, Interleukin-2; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Cladribine; Hairy cell leukemia; IL28B polymorphism; Interferon-alpha; Soluble interleukin-2 receptor