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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3777-3784. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-1173. This Article Full Text (PDF) All Versions of this Article: 2005-03-1173v1 106/12/3777    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 Lonial, S. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Lonial, S. Articles by Anderson, K. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 23, 2005 Accepted August 1, 2005 Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma Sagar Lonial*, Edmund K Waller, Paul G Richardson, Sundar Jagannath, Robert Z Orlowski, Cynthia R Giver, David L Jaye, Dixil Francis, Sara Giusti, Claire Torre, Bart Barlogie, James R Berenson, Seema Singhal, David P Schenkein, Dixie-Lee W Esseltine, Jessica Anderson, Hugh Xiao, Leonard T Heffner, and Kenneth C Anderson Winship Cancer Institute, Emory University, Atlanta, GA, USA Dana Farber Cancer Institute, Boston, MA, USA St. Vincent's Comprehensive Cancer Center, New York, NY, USA University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Myeloma and Transplant Research Center, Arkansas Cancer Research Center, Little Rock, AK, USA Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA Northwestern University, Chicago, IL, USA Millennium Pharmaceuticals, Inc., Cambridge, MA, USA * Corresponding author; email: sloni01{at}emory.edu. Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in two phase II trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclical fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Serum thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown, but it is unlikely to be related to marrow injury or decreased thrombopoietin production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. Berenson, O. Yellin, R. Patel, H. Duvivier, Y. Nassir, R. Mapes, C. D. Abaya, and R. A. Swift A Phase I Study of Samarium Lexidronam/Bortezomib Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res., February 1, 2009; 15(3): 1069 - 1075. 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