Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival Ulla Olsson-Stro¨mberg* ,1 , Bengt Simonsson 1 , Tomas Ahlgren 2 , Magnus Bjo¨rkholm 3 , Karin Carlsson 4 , Go¨sta Gahrton 5 , Robert Hast 3 , Eva Lo¨fvenberg 6 , Olle Linder 7 , Per Ljungman 5 ,ClaesMalm 4 ,ChristerPaul 5 ,StigRo¨djer 8 ,IngemarTuresson 2 ,Ann-MariUde´n 5 , Anders Wahlin 6 , Andreas Killander 1 , Bengt Wadman 7 , Jan Westin 8 , Olle Vikrot 7 , Olle Zettervall 2 , Gunnar O ¨ berg 1 for the Swedish CML Study group 1 Departments of Medicine and Hematology, University Hospital, Uppsala, Sweden; 2 Malmo ¨ University Hospital, Malmo ¨, Sweden; 3 Karolinska University Hospital, Stockholm, Sweden; 4 University Hospital, Linko ¨ping, Sweden; 5 Huddinge University Hospital, Stockholm, Sweden; 6 University Hospital, Umea ˚, Sweden; 7 University Hospital, O ¨ rebro, Sweden; 8 East Hospital, Gothenburg, Sweden Introduction: Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known; to follow up the long-time outcome of this treatment was therefore of great interest. Materials and methods: Previously untreated CML patients were randomly started on either hydroxyurea (30mg/kg/day) or busulphan (0.1mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. Results: A total of 179 patients were randomised, 90 to hydroxyurea, and 89 to busulphan treatment.Therewasnosignificantdifferenceinsurvivalbetweenhydroxyurea-andbusulphan- treated patients (P ¼ 0.46); median survival was 3.5 and 3.2 years, respectively. Inall,85ofthepatientsweresubsequentlydiagnosedwithblastcrisis,41inthebusulphanand 44 in the hydroxyurea group. There was no significant difference between the two groups (P ¼ 0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P ¼ 0.0001). The 5-year-survival rates were 50 and 22% and the 10-year- survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. Conclusion: We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival; transplanted patients survived significantly longer than nontransplanted patients. The Hematology Journal (2004) 5, 462–466. doi:10.1038/sj.thj.6200552 Keywords: chronic myeloid leukaemia; randomised; hydroxyurea; busulphan; bone marrow transplantation Introduction Chronic myeloid leukaemia (CML) is a clonal myelo- proliferative disease of haematopoietic stem cells. It is characterised by an initial chronic phase followed by a progression to accelerated phase and finally to blast crisis.Theeffectthatconventionalchemotherapyhason time to blast crisis is marginal; symptoms are, however, relieved. More aggressive treatment, including high- dose chemotherapy and high-dose interferon, seems to benefit survival but produces more pronounced side effects. 1–5 Imatinibmesylate(Glivec s Novartis)isanew, promising and well-tolerated drug used in both chronic and accelerated phase. 6–8 The only known curative treatment for CML is allogeneic stem cell transplanta- tion(BMT).Although,imatinibmesylateandinterferon Received 2 January 2004; accepted 15 July 2004 *Correspondence: U Olsson-Stro¨mberg, Department of Internal Medicine, University Hospital, SE-751 85 Uppsala, Sweden; Tel: þ 46 18 61 10 00; Fax: þ 46 18 51 01 33; E-mail: ulla.olsson.stromberg@medicin.uas.lul.se or ulla.stromberg@talk21.com The Hematology Journal (2004) 5, 462–466 & 2004 The European Hematology Association All rights reserved 1466-4680/04 $30.00 www.nature.com/thj