title: Evaluation of beta globin mRNA as an early marker of haemoglobin response to epoetin treatment.
abstract: Approximately 60% of anaemic cancer patients respond to epoetin treatment. An early marker of response would be valuable in order to avoid ineffective treatment. We have previously shown that beta globin mRNA increases rapidly after epoetin beta treatment of healthy controls. In the present study we have evaluated whether a change of this marker during the first 2 weeks of epoetin treatment could predict later Hb response in anaemic cancer patients. Twenty cancer patients with Hb <11 g/dl received epoetin beta (NeoRecormon) 10,000 IU three times weekly during 6 weeks. Hb, reticulocytes and beta-globin mRNA were followed. The latter was measured quantitatively using PCR via the 5' nuclease assay. Eleven patients responded with a Hb increase of >1 g/dl, nine were nonresponders. All responders increased in beta-globin mRNA within 2 weeks, mean 7.7 x base-line. With a cut-off of an increase of 3 x base-line value, we obtained a specificity of 45% and a sensitivity of 91% for the prediction of a later increase of Hb >1 g/dl. With a cut-off of 4x base-line, the specificity increased to 66%, but the sensitivity decreased to 82%. Beta globin mRNA increases before Hb in all responding patients. However, some non-responding patients also show an increase, and there is a trade-off between specificity and sensitivity as the cut-off level is set at different levels. Compared to reticulocyte count, beta-globin mRNA is more reliable in the individual patient, but the clinical usefulness of the assay needs to be evaluated in further studies.
authors.affiliation: Department of Haematology, University Hospital, Uppsala 751 85, Sweden. gunnar.birgegard@medsci.uu.se
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegård
authors.forename: Fredrik
authors.initials: F
authors.lastname: Dahl
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Ulf
authors.initials: U
authors.lastname: Landegren
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D001609:Beta-Globulins / Q000187:drug effects* / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D004921:Erythropoietin / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000150:complications; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D012156:Reticulocytes / Q000166:cytology; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D001609:Beta-Globulins; D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin