|
|
Blood, 15 March 2004, Vol. 103, No. 6, pp. 2027-2031.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2002-10-3270.
Submitted October 29, 2002
Accepted October 27, 2003
Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia
Andy C Rawstron*, Ben Kennedy, Paul Moreton, Anita J Dickinson, Matthew J Cullen, Stephen J Richards, Andrew S Jack, and Peter Hillmen
Academic Unit of Haematology and Oncology, HMDS, Leeds General Infirmary, Leeds, United Kingdom
* Corresponding author; email: andy.rawstron{at}hmds.org.uk.
Alemtuzumab therapy is effective for some refractory CLL, but identifying responders requires at least eight weeks of therapy. Early identification of non-responders would minimise 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 and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis resolved in all patients by week four, significant depletion of bone marrow tumour only occurred if circulating B-lymphocytes were persistently <0.001 x109/L, which was rare in non-responders. 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 algorithm: peripheral B-cell count >0.001 x109/L at week two with <1 log depletion of circulating B-cells between weeks two and four. Monitoring CLL levels post-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 tumour, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at two and four weeks may be used to optimise therapy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Bottcher, M. Ritgen, S. Buske, S. Gesk, W. Klapper, E. Hoster, W. Hiddemann, M. Unterhalt, M. Dreyling, R. Siebert, et al.
Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations
Haematologica,
April 1, 2008;
93(4):
551 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Caballero, J. A. Garcia-Marco, R. Martino, V. Mateos, J. M. Ribera, J. Sarra, A. Leon, G. Sanz, J. de la Serna, R. Cabrera, et al.
Allogeneic Transplant with Reduced Intensity Conditioning Regimens may Overcome the Poor Prognosis of B-Cell Chronic Lymphocytic Leukemia with Unmutated Immunoglobulin Variable Heavy-Chain Gene and Chromosomal Abnormalities (11q- and 17p-)
Clin. Cancer Res.,
November 1, 2005;
11(21):
7757 - 7763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Elter, P. Borchmann, H. Schulz, M. Reiser, S. Trelle, R. Schnell, M. Jensen, P. Staib, T. Schinkothe, H. Stutzer, et al.
Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial
J. Clin. Oncol.,
October 1, 2005;
23(28):
7024 - 7031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Haferlach, A. Kohlmann, S. Schnittger, M. Dugas, W. Hiddemann, W. Kern, and C. Schoch
Global approach to the diagnosis of leukemia using gene expression profiling
Blood,
August 15, 2005;
106(4):
1189 - 1198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
