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

• Published in: Cancer Vol. 115; no. 1; pp. 94 - 100
• Main Authors: ROBAK, Tadeusz, BLONSKI, Jerzy Z, WAWRZYNIAK, Ewa, GORA-TYBOR, Joanna, PALACZ, Aleksandra, DMOSZYNSKA, Anna, KONOPKA, Lech, WARZOCHA, Krzysztof, JAMROZIAK, Krzysztof
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 2009
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chromosomes, Human, Pair 17; Cladribine - administration & dosage; Cladribine - adverse effects; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Drug Administration Schedule; Female; Genes, p53; Hematologic and hematopoietic diseases; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Retrospective Studies; Sequence Deletion; Tumors; Poland; Europe; Antineoplastic agent; Purine nucleoside; Deoxyribonucleoside; p53; Cancerology; TP53 Gene; Lymphoproliferative syndrome; Deletion; Adult; Tumor suppressor gene; Human; 17p13 deletion; Drug combination; Malignant hemopathy; Biological activity; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Chronic lymphocytic leukemia; Antimetabolic; Chromosome E17; Nitrogen mustard; Cladribine; Combined treatment; TP53; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24003

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.