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Revista Argentina de Hematología

Abstract

Volumen:    22    # Number : 1

Publication Date :    Enero - Abril    Year:    2018

   ARTÍCULO ORIGINAL

Prognostic significance of the percentage of 13q14 deletion in patients with chronic lymphocytic leukemia

Authors: Palau Nagore V, Brizuela B, Giere I, Stella F, Stanganelli C, Bezares R, Rodríguez A, Pavlovsky C, Pavlovsky MA, Slavutsky I.

Abstract: Genomic alterations are one of most important prognostic factors in chronic lymphocytic leukemia (CLL). Among them, 13q14 deletion (del13q14) is the most frequent genetic anomaly, associated to a favorable prognosis when it is a sole alteration. However, data of the literature support that patients with isolated del13q14 do not constitute a homogeneous group. Different studies suggest a relatively worse clinical behavior for patients carrying higher percentages of del13q14 nuclei, with results ranging between 60% to 85% abnormal leukemic cells. In this study, we have evaluated the percentage of leukemic cells with isolated del13q14 in CLL patients in order to identify subsets with a different progression risk. A total of 65 CLL cases with isolated del13q14 by interphase FISH, were studied. Chromosome analysis was performed on stimulated peripheral blood lymphocytes cultures. FISH study was performed using the CLL panel according to manufacturer´s protocol. IGHV (immunoglobulin heavy chain variable region) mutational status was analyzed by RT-PCR and bidirectional sequencing. The study was approved by the local Ethics Committees. All individuals provided their written informed consent. By FISH, the median percentage of nuclei with del13q14 was 57.5% (range: 13%-98%). A monoallelic deletion was observed in 48 cases (73.8%) while 17 (26.2%) patients showed a biallelic condition. The distribution of cases according to the percentage of cells with del13q14 was: 11%-40% (17), 41%- 70% (21) and 71%-100% (27). Statistical analysis identified 70% of nuclei carrying del13q14 as the most appropriate cutoff in our series. The analysis of clinical characteristics showed significant increase of white blood cells count (p=0.01), percentage of lymphocytes (p=0.009) and Beta 2 microglobuline (p=0.011) as well as a decrease in the hemoglobin levels (p=0.006) in cases with >70% of deleted nuclei compared to those with <70%. In addition, a significantly short treatment free survival (TFS) was observed in the cohort of patients with losses of 13q14 in more than 70% of cells (54.5 months) compared to those with <70% of abnormal nuclei (98 months) (p<0.05). To our knowledge, this is the first study about the clinical significance of the percentage of leukemic cells with del13q14 in CLL patients in our country. Our results showed significant differences in clinical parameters as well as a shorter TFS for patients with more than 70% of cells with this alteration, providing a reference value for clinical practice and contributing to the biological characterization of the disease.

Key words: chronic lymphocytic leukemia, 13q14 deletion, clinical evolution.

Pages : 21-27

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