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.

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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.

Tadeusz Robak, Jerzy Z Blonski, Ewa Wawrzyniak, Joanna Gora-Tybor, Aleksandra

Palacz, Dmoszynska, Lech Konopka, Krzysztof Warzocha, and Krzysztof

Jamroziak

Cancer, November 24, 2008; .

Department of Hematology, Medical University of Lodz, Lodz, Poland.

BACKGROUD:: 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.

METHODS:: 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/m(2)

given intravenously for 3 consecutive days. The CC cycles were repeated at

28-day intervals for up to 6 cycles. RESULTS:: 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%).

CONCLUSIONS:: 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.

PMID: 19025975