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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1820-1826. Prepublished online as a Blood First Edition Paper on November 30, 2007; DOI 10.1182/blood-2007-07-101303. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-07-101303v1 111/4/1820    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dearden, C. Articles by Catovsky, D. Search for Related Content PubMed PubMed Citation Articles by Dearden, C. Articles by Catovsky, D. Related Collections Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia Claire Dearden1, Rachel Wade2, Monica Else1, Sue Richards2, Don Milligan3, Terry Hamblin4, Daniel Catovsky1, for the UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group and NCRI CLL Working Group 1 Royal Marsden National Health Service (NHS) Foundation Trust and Institute of Cancer Research, Sutton; 2 Clinical Trial Service Unit, Oxford; 3 Birmingham Heartlands Hospital, Birmingham; and 4 Royal Bournemouth Hospital, Bournemouth, United Kingdom Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to examine the prognostic impact of both a positive direct antiglobulin test (DAT) and AHA. Seven-hundred seventy-seven patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC). The incidence pretreatment of a positive DAT was 14%. Ten percent developed AHA. The DAT correctly predicted the development, or not, of AHA after therapy in 83% of cases, however only 28% of DAT-positive patients developed AHA. Of 299 patients tested both before and after treatment, those treated with single-agent fludarabine were most likely to remain DAT positive and to change from negative to positive. Patients treated with chlorambucil or fludarabine were more than twice as likely to develop AHA as those receiving FC. In a multivariate analysis, stage C disease and high β2 microglobulin were independent predictors of a positive DAT result. AHA, or a positive DAT, with or without AHA, independently predicted for reduced overall survival (OS). Four deaths, all on fludarabine monotherapy, were attributed to AHA. In conclusion, DAT status at the time of initiation of therapy provides a new prognostic indicator, although FC may protect against AHA. This trial was registered at http://isrctn.org as no. 58585610. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: DAT ± AHA = bad CLL Martin J. S. Dyer Blood 2008 111: 1757. [Full Text] [PDF] This article has been cited by other articles: L. E Glance, A. Cumpston, A. Kanate, and S. C Remick Bendamustine-Associated Hemolytic Anemia Ann. Pharmacother., November 1, 2009; 43(11): 1903 - 1906. [Abstract] [Full Text] [PDF] S MacCallum, M Groves, D Brass, J Cunningham, M Sales, K Gelly, and S Tauro Autoimmune pancytopenia following combination chemotherapy for chronic lymphocytic leukaemia J. Clin. Pathol., May 1, 2009; 62(5): 468 - 470. [Abstract] [Full Text] [PDF] J. Galletti, C. Canones, P. Morande, M. Borge, P. Oppezzo, J. Geffner, R. Bezares, R. Gamberale, and M. Giordano Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia J. Immunol., September 1, 2008; 181(5): 3674 - 3683. [Abstract] [Full Text] [PDF] C. Dearden Disease-Specific Complications of Chronic Lymphocytic Leukemia Hematology, January 1, 2008; 2008(1): 450 - 456. [Abstract] [Full Text] [PDF]

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