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Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia

Rawstron, A.C., Kennedy, B., Moreton, P., Dickinson, A.J., Cullen, M.J., Richards, S.J., Jack, A.S. and Hillmen, P. (2004) Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia. Blood, 103 (6). pp. 2027-2031. ISSN 0006-4971

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Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 109/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 109/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Health Sciences (York)
Depositing User: York RAE Import
Date Deposited: 25 Aug 2009 17:01
Last Modified: 25 Aug 2009 17:01
Published Version: http://dx.doi.org/10.1182/blood-2002-10-3270
Status: Published
Publisher: American Society of Hematology
Identification Number: 10.1182/blood-2002-10-3270
URI: http://eprints.whiterose.ac.uk/id/eprint/5710

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