Triapine® is a potent ribonucleotide reductase (RR) inhibitor that depletes intracellular deoxyribonculeotide pools, especially dATP. We designed a Phase I trial of Triapine followed by the adenosine analog fludarabine in adults with refractory acute leukemias and aggressive myeloproliferative disorders (MPD). Two schedules were examined: A. Triapine 105mg/m 2 /day over 4 hours followed by fludarabine daily × 5 (24 patients, fludarabine 15-30 mg/m 2 /dose); B.To whom correspondence should be addressed: Judith E. Karp, MD, Sidney Kimmel Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB Room 289, Baltimore, Maryland 21231-1000, Phone: 410-502-7726, Fax: 410-614-1005.edu. Current affiliation:Yale University School of Medicine, New Haven, CT Current affiliation: Genentech, South San Francisco, CA Contributions: J.E. Karp contributed to concept and design; performed research; collected, interpreted and analyzed data; wrote the paper; provided intellectual content and provided study material/patients. F.J. Giles, I. Gojo, and L.E. Morris performed research; collected, interpreted and analyzed data; provided intellectual content; and provided study material/patients. J. Greer and M. Thein collected and/ or assembled data. M. Sznol contributed to concept and design and provided intellectual content. J. Low contributed to data analysis and provided intellectual content.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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