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Activity of cladribine combined with cyclophosphamide in frontline therapy for chronic lymphocytic leukemia with 17p13.1/TP53 deletion†
Report From the Polish Adult Leukemia Group
Article first published online: 24 NOV 2008
Copyright © 2008 American Cancer Society
Volume 115, Issue 1, pages 94–100, 1 January 2009
How to Cite
Robak, T., Blonski, J. Z., Wawrzyniak, E., Gora-Tybor, J., Palacz, A., Dmoszynska, A., Konopka, L., Warzocha, K. and Jamroziak, K. (2009), Activity of cladribine combined with cyclophosphamide in frontline therapy for chronic lymphocytic leukemia with 17p13.1/TP53 deletion. Cancer, 115: 94–100. doi: 10.1002/cncr.24003
The following individuals contributed to this article, Bogdan Kaluzewski, MD, PhD and Maria Constantinou, PhD (Department of Medical Genetics, Medical University of Lodz, Lodz, Poland); Barbara Pienkowska-Grela, PhD (Department of Medical Genetics, Institute of Oncology, Warsaw, Poland); Dorota Koczkodaj, PhD (Department of Medical Genetics, Medical University of Lublin, Lublin, Poland); Malgorzata Kowal, MD, PhD (Department of Hematology, Medical University of Lublin, Lublin, Poland); Bernadetta Ceglarek, MD, PhD (Department of Internal Medicine and Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland); and Ilona Seferynska, MD, PhD (Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland).
- Issue published online: 29 DEC 2008
- Article first published online: 24 NOV 2008
- Manuscript Accepted: 6 AUG 2008
- Manuscript Revised: 27 JUL 2008
- Manuscript Received: 20 JUN 2008
- Ministry of Science, Warsaw Poland. Grant Number: 2P05B01828
- Medical University of Lodz. Grant Number: 503-1093-1
- Foundation for the Development of Diagnostics and Therapy, Warsaw, Poland
- chronic lymphocytic leukemia;
- 17p13 deletion;
The 17p13.1 deletion that causes loss of the p53-encoding TP53 gene is the most powerful predictor of a poor response to conventional therapy and shortened survival in patients with chronic lymphocytic leukemia (CLL). The results of this study have demonstrated that the cladribine and cyclophosphamide regimen may improve treatment results in this poor-risk patient population.
In this study, the authors retrospectively analyzed the efficacy and toxicity of 2-CdA with cyclophosphamide combination (the CC regimen) in 20 patients with previously untreated B-cell CLL who had 17p13.1 deletion reported to the Polish Adult Leukemia Group (PALG) registry. The CC regimen consisted of 2-CdA at a dose of 0.12 mg/kg and cyclophosphamide at a dose of 250 mg/m2 given intravenously for 3 consecutive days. The CC cycles were repeated at 28-day intervals for up to 6 cycles.
Overall, 16 of 20 patients (80%) responded to CC therapy, including 10 patients (50%) who obtained a complete response and 6 patients (30%) who obtained a partial response. The median progression-free survival reached 23 months (95% confidence interval, 5-41 months). The overall survival probability at 2 years was 52.5% (95% confidence interval, 26%-79%). Treatment toxicity generally was acceptable. Infections were the most common grade 3/4 complications and occurred in 6 patients (30%).
In this retrospective analysis, the results demonstrated that the CC regimen produced a relatively high response rate in patients with previously untreated CLL who had 17p13.1/TP53 deletion, although the response duration and survival were not satisfactory. It is possible that a combination of the CC regimen with p53-independent agents may improve treatment results in this poor-risk patient population. Cancer 2009. © 2008 American Cancer Society.