1. ¹Cleveland Clinic Foundation, Myeloma Program, Cleveland, OH, USA
2. ²Department of Pathology, Southwest Oncology Group Statistical Center, Seattle, WA, USA
3. ³Department of Internal Medicine, Division of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN, USA
4. ⁴Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico, Albuquerque, NM, USA
5. ⁵Department of Medicine, Division of Hematology, University of Cincinnati, Cincinnati, OH, USA
6. ⁶Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA
7. ⁷Scott & White Hospital, Temple, TX, USA
8. ⁸Taussig Cancer Center, Wichita Community Clinical Oncology Program, Wichita, KS, USA
9. ⁹Puget Sound Oncology Consortium, Seattle, WA, USA

Correspondence: Dr MA Hussein, Southwest Oncology Group (S9706), Operations Office, 14980 Omicron Drive, San Antonio, Texas 78245-3217, USA. Fax: +1 216 445 3434; E-mail: pubs@swog.org

Received 2 August 2004; Accepted 12 July 2005; Published online 29 September 2005.

Abstract

B-cell chronic lymphocytic leukemia (CLL) accounts for 95% of chronic leukemia cases and 25% of all leukemia. Despite the prevalence of CLL, progress in its treatment has been only modest over the past three decades. Based upon the ability of fludarabine to produce high-grade remissions especially among patients with low initial tumor mass, and the ability of alkylators to reduce tumor mass, we hypothesized that sequential administration of a limited number of cycles of intermediate-dose cyclophosphamide followed by fludarabine could result in a larger percentage of patients with complete remissions (CRs). In all, 27 of the 49 eligible patients achieved overall responses of CR, unconfirmed complete remission (UCR), or PR, for a total response rate of 55% (95% confidence interval (CI) 40–69%). Considering the confounding medical issues of this patient population with advanced aggressive disease, the regimen was generally well tolerated. This study demonstrates that high-dose cyclophosphamide followed by fludarabine was relatively well tolerated in this group of advanced CLL patients. The study's criterion for testing whether the regimen is sufficiently effective to warrant further investigation was met: 14 (32%) of the first 44 eligible patients achieved CR or UCR.