Leukemia Research 27 (2003) 405–411 A randomized study comparing interferon (IFN) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML) T. Kühr a,* , S. Burgstaller a , U. Apfelbeck b , W. Linkesch b , H. Seewann c , M. Fridrik d , G. Michlmayr e , O. Krieger f , D. Lutz f , W. Lin g , J. Pont h , L. Köck i , K. Abbrederis j , C. Baldinger a , R. Buder k , D. Geissler l , H. Hausmaninger m , A. Lang n , A. Zabernigg o , C. Duba p , W. Hilbe q , W. Eisterer q , M. Fiegl q , R. Greil q , G. Gastl q , J. Thaler a , for the Austrian CML Study Group a Department of Internal Medicine, General Hospital, Grieskirchnerstr. 42, Wels A-4600, Austria b Department of Internal Medicine, University Hospital, Graz, Austria c Department of Internal Medicine, General Hospital, Fürstenfeld, Austria d Department of Internal Medicine, General Hospital, Linz, Austria e Department of Internal Medicine, Hospital of the Sisters of Mercy, Linz, Austria f Department of Internal Medicine, Hospital of the Elizabethans, Linz, Austria g Department of Internal Medicine, State Hospital, Villach, Austria h Department of Internal Medicine, Kaiser Franz Josef Hospital, Wien, Austria i Department of Internal Medicine, County Hospital, Lienz, Austria j Department of Internal Medicine, Municipal Hospital, Dornbirn, Austria k Department of Internal Medicine, Hospital of the Brothers of Mercy, Linz, Austria l Department of Internal Medicine, State Hospital, Klagenfurt, Austria m Department of Internal Medicine, State Hospital, Salzburg, Austria n Department of Internal Medicine, State Hospital, Feldkirch, Austria o Department of Internal Medicine, County Hospital, Kufstein, Austria p Department of Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, Austria q Department of Internal Medicine, University Hospital Innsbruck, Innsbruck, Austria Received 13 September 2002; accepted 28 September 2002 Abstract This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN-2c (3.5 MU/d) in combination with either araC (10 mg/m 2 d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1–73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities. © 2003 Elsevier Science Ltd. All rights reserved. Keywords: CML; Interferon; Hydroxyurea; Cytarabine; Randomised study 1. Introduction Chronic myeloid leukemia (CML) is a clonal disorder arising in an early hematopoietic progenitor cell. It starts with acquisition of the Philadelphia (Ph) chromosome translocation (t(9;22)), which generates a chimeric tyrosine- * Corresponding author. Tel.: +43-7242-415-9-3454. E-mail address: thomas.kuehr@khwels.at (T. Kühr). specific protein kinase gene (bcr-abl). The final product of this genetic rearrangement is responsible for most pheno- typic abnormalities of chronic phase CML. Allogeneic bone marrow transplantation (BMT) is the only therapeutic procedure able to cure a substantial propor- tion of patients with CML. Since allogeneic BMT is depen- dent on age and the patient’s donor type, it can be offered to only a limited number of patients. Thus, for the majority of patients a conservative treatment approach has to be persued. 0145-2126/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. PII:S0145-2126(02)00223-0