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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1923-1930. Prepublished online as a Blood First Edition Paper on June 24, 2008; DOI 10.1182/blood-2007-05-092882. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-05-092882v1 112/5/1923    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Rassenti, L. Z. Articles by Kipps, T. J. PubMed PubMed Citation Articles by Rassenti, L. Z. Articles by Kipps, T. J. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia Laura Z. Rassenti1,2, Sonia Jain1,3, Michael J. Keating1,4, William G. Wierda1,4, Michael R. Grever1,5, John C. Byrd1,5, Neil E. Kay1,6, Jennifer R. Brown1,7, John G. Gribben1,8, Donna S. Neuberg1,7, Feng He1,3, Andrew W. Greaves1,2, Kanti R. Rai1,9, and Thomas J. Kipps1,2 1 The Chronic Lymphocytic Leukemia Research Consortium, La Jolla, CA; 2 Division of Hematology/Oncology, Department of Medicine, University of California, San Diego and Moores UCSD Cancer Center, La Jolla; 3 Division of Biostatistics and Bioinformatics, University of California, San Diego; 4 Department of Leukemia, the University of Texas M. D. Anderson Cancer Center, Houston; 5 James Cancer Institute, Ohio State University, Columbus; 6 Department of Hematology, Mayo Clinic, Rochester, MN; 7 Dana-Farber Cancer Institute, Boston, MA; 8 Barts and The London School of Medicine, London, United Kingdom; and 9 Long Island Jewish Medical Center, New Hyde Park, NY Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70–negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70–positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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