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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2908-2913. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-07-2195. This Article Full Text (PDF) Erratum (v104,p42) All Versions of this Article: 2003-07-2195v1 103/8/2908    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ossenkoppele, G. J Articles by Verhoef, G. E Search for Related Content PubMed PubMed Citation Articles by Ossenkoppele, G. J Articles by Verhoef, G. E Social Bookmarking                   What's this? Submitted July 8, 2003 Accepted November 17, 2003 The value of Fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high risk myelodysplastic syndromes and elderly AML Gert J Ossenkoppele*, Wilfried J Graveland, Pieter Sonneveld, Simon M Daenen, Douwe H Biesma, Leo F Verdonck, M R Schaafsma, Petra H Westveer, G J Peters, Paul Noordhuis, Petra Muus, B van de Holt, M Delforge, Bob Lowenberg, and Gregor E Verhoef Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands HOVON Data Center, Erasmus Medical Center, Rotterdam, The Netherlands Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Hematology, Academic Hospital, Groningen, The Netherlands Department of Hematology, St Antonius Ziekenhuis, Nieuwegein, The Netherlands Department of Hematology, University Medical Center, Utrecht, The Netherlands Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands Department of Hematology, University Medical Center, Nijmegen, The Netherlands Department of Hematology, University Hospitals K. U., Leuven, The Netherlands * Corresponding author; email: g.ossenkoppele{at}vumc.nl. Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-CTP, responsible for the cytotoxic effect in leukemic blasts. In a randomized Phase III trial patients with high risk MDS (n=91) or elderly AML (n=43) were randomized to receive two induction courses consisting of ARA-C (2 g/m2 days 1-5) and G-CSF (filgrastim, 5µg/kg) during and after chemotherapy with or without Fludarabine (25 mg/m2 days 1-5) (FLAG vs. AG). Consolidation consisted of Daunorubicin (45 mg/m2 days 1-3) and ARA-C (200 mg/m2 days 1-7). CR rate following AG was 65% versus 71% with FLAG (p=0.49). OS at 24 months was for AG treatment 24% and 39% for FLAG (p=0.32). EFS at 2 years was 10% and 19% (p=0.31) respectively. Platelet and granulocyte recovery times after the second cycle were prolonged in the FLAG treatment group. Grade 3-4 neurotoxicities were more often reported in the FLAG arm (14% vs 3%, p=0.03) while no significant differences in other toxicities were observed. In a cohort of patients the in vivo accumulation of ARA-CTP in leukemic cells was determined. Although ARA-CTP accumulation in leukemic cells after FLAG was enhanced, clinical outcome in terms of CR rate, OS, EFS and DFS was not significantly improved by combining Fludarabine with ARA-C. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. V. Rao, P. J.M. Valk, K. H. Metzeler, C. R. Acharya, S. A. Tuchman, M. M. Stevenson, D. A. Rizzieri, R. Delwel, C. Buske, S. K. Bohlander, et al. Age-Specific Differences in Oncogenic Pathway Dysregulation and Anthracycline Sensitivity in Patients With Acute Myeloid Leukemia J. Clin. Oncol., November 20, 2009; 27(33): 5580 - 5586. [Abstract] [Full Text] [PDF] H. J. M. de Jonge, E. S. J. M. de Bont, P. J. M. Valk, J. 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