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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1276-1283.
Prepublished online as a Blood First Edition Paper on October 4, 2005; DOI 10.1182/blood-2005-02-0819.
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Submitted March 1, 2005
Accepted September 7, 2005
How we treat refractory chronic lymphocytic leukemia
Emili Montserrat*, Carol Moreno, Jordi Esteve, Alvaro Urbano-Ispizua, Eva Gine, and Francesc Bosch
Institute of Hematology and Oncology, Department of Hematology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Hospital Clinic, Barcelona, Spain
* Corresponding author; email: emontse{at}clinic.ub.es.
Therapy of patients with CLL has greatly changed over the past few years. After years of stagnation, with treatment revolving around the use of rather ineffective drugs such as alkylators, many patients are now being treated with more effective agents such as purine analogs either alone or combined with other drugs and/or monoclonal antibodies. Treatment of patients refractory to these treatments is particularly challenging and should be decided upon a careful evaluation of the disease, patient's characteristics, and prognostic factors. Refractory disease should be clearly separated from relapsing disease. The only curative therapy for patients with CLL, including those with refractory disease, is allogeneic stem cell transplantation. However, the use of allogeneic transplantation is limited because of the advanced age of most patients and the high transplant-related mortality (TRM). Transplants with non-myeloablative regimens may reduce TRM and to allow to transplant more patients, more safely. For patients in whom an allogeneic transplantation is not feasible or it is deemed inappropriate, participation in phase II trials should be encouraged. Finally, to investigate mechanisms to overcome resistance to therapy in CLL and to identify patients that might gain benefit from early, intensive therapies (e.g., based on biological markers) constitute a challenge that needs active investigation.

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