Impact of gene mutations and chromosomal aberrations on
progression-free survival in chronic lymphocytic leukemia
patients treated with front-line chemoimmunotherapy: Clinical
practice experience

J 2019

Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience

ŠPUNAROVÁ, Michaela, Nikola TOM, Šárka PAVLOVÁ, Marek MRÁZ, Yvona BRYCHTOVÁ et. al.

Basic information

Original name

Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience

Authors

ŠPUNAROVÁ, Michaela (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Marek MRÁZ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Hana SKUHROVÁ FRANCOVÁ (203 Czech Republic, belonging to the institution), Anna BRZOBOHATÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Martin TRBUŠEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Leukemia Research, Oxford, PERGAMON-ELSEVIER SCIENCE LTD, 2019, 0145-2126

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.214

RIV identification code

RIV/00216224:14110/19:00108468

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.leukres.2019.04.015

UT WoS

000468184500012

Keywords in English

CLL; chemoimmunotherapy; deletion 11q22; IGHV; BIRC3; ATM

Abstract

V originále

The impact of genetic aberrations on rituximab-based therapeutic regimens has been intensely studied in chronic lymphocytic leukemia (CLL). According to the current consensus chemoimmunotherapy consisting of rituximab and DNA-damaging drugs is not suitable for patients with TP53 defects. In our study, we focused on CLL patients with an intact TP53 gene and investigated four recurrently mutated genes in CLL, genomic aberrations by FISH, and IGHV status with the aim of analyzing their impact on progression-free survival (PFS) after front-line therapy with FCR (fludarabine, cyclophosphamide, rituximab) or BR (bendamustine, rituximab) regimens. Using next-generation sequencing, we analyzed 120 patients treated with FCR and 57 patients treated with BR at a university hospital. We used a 10% cut-off for variant allele frequency and recorded the following mutation frequencies in the pre-therapy samples: ATM 23%, SF3B1 20%, NOTCH1 19% and BIRC3 11%. The data on cytogenetic aberrations (11q22, 13q14, trisomy 12) and IGHV mutation status were also considered in PFS analyses. In univariate analyses, we observed a negative impact of BIRC3 mutations and 11q22 deletion in both regimens, while the unmutated IGHV status was associated with a significantly shorter PFS only in the FCR-treated cohort. In a multivariate analysis, only deletion 11q22 in both regimens, and the unmutated IGHV in the FCR cohort maintained an independent association with the reduced PFS. Notably, sole 11q22 deletion, without an ATM mutation on the other allele, manifested the shortest PFS of all analyzed markers. Deletion 11q22 and IGHV status predict PFS in previously untreated CLL patients.

Links

NV16-32743A, research and development project

Name: Prediktivní stratifikace pacientů s CLL pro terapie využívající monoklonální protilátky cílené na antigen CD20

Citovat

ŠPUNAROVÁ, Michaela, Nikola TOM, Šárka PAVLOVÁ, Marek MRÁZ, Yvona BRYCHTOVÁ, Michael DOUBEK, Anna PANOVSKÁ, Hana SKUHROVÁ FRANCOVÁ, Anna BRZOBOHATÁ, Šárka POSPÍŠILOVÁ, Jiří MAYER and Martin TRBUŠEK. Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience (Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: clinical practice experience). Leukemia Research. Oxford: PERGAMON-ELSEVIER SCIENCE LTD, 2019, vol. 81, JUN 2019, p. 75-81. ISSN 0145-2126. Available from: https://dx.doi.org/10.1016/j.leukres.2019.04.015.

@article{1531396,
   author = {Špunarová, Michaela and Tom, Nikola and Pavlová, Šárka and Mráz, Marek and Brychtová, Yvona and Doubek, Michael and Panovská, Anna and Skuhrová Francová, Hana and Brzobohatá, Anna and Pospíšilová, Šárka and Mayer, Jiří and Trbušek, Martin},
   article_location = {Oxford},
   article_number = {JUN 2019},
   doi = {http://dx.doi.org/10.1016/j.leukres.2019.04.015},
   keywords = {CLL; chemoimmunotherapy; deletion 11q22; IGHV; BIRC3; ATM},
   language = {eng},
   issn = {0145-2126},
   journal = {Leukemia Research},
   title = {Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience},
   url = {http://dx.doi.org/10.1016/j.leukres.2019.04.015},
   volume = {81},
   year = {2019}
}

TY  - JOUR
ID  - 1531396
AU  - Špunarová, Michaela - Tom, Nikola - Pavlová, Šárka - Mráz, Marek - Brychtová, Yvona - Doubek, Michael - Panovská, Anna - Skuhrová Francová, Hana - Brzobohatá, Anna - Pospíšilová, Šárka - Mayer, Jiří - Trbušek, Martin
PY  - 2019
TI  - Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience
JF  - Leukemia Research
VL  - 81
IS  - JUN 2019
SP  - 75-81
EP  - 75-81
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 01452126
KW  - CLL
KW  - chemoimmunotherapy
KW  - deletion 11q22
KW  - IGHV
KW  - BIRC3
KW  - ATM
UR  - http://dx.doi.org/10.1016/j.leukres.2019.04.015
L2  - http://dx.doi.org/10.1016/j.leukres.2019.04.015
N2  - The impact of genetic aberrations on rituximab-based therapeutic regimens has been intensely studied in chronic lymphocytic leukemia (CLL). According to the current consensus chemoimmunotherapy consisting of rituximab and DNA-damaging drugs is not suitable for patients with TP53 defects. In our study, we focused on CLL patients with an intact TP53 gene and investigated four recurrently mutated genes in CLL, genomic aberrations by FISH, and IGHV status with the aim of analyzing their impact on progression-free survival (PFS) after front-line therapy with FCR (fludarabine, cyclophosphamide, rituximab) or BR (bendamustine, rituximab) regimens. Using next-generation sequencing, we analyzed 120 patients treated with FCR and 57 patients treated with BR at a university hospital. We used a 10% cut-off for variant allele frequency and recorded the following mutation frequencies in the pre-therapy samples: ATM 23%, SF3B1 20%, NOTCH1 19% and BIRC3 11%. The data on cytogenetic aberrations (11q22, 13q14, trisomy 12) and IGHV mutation status were also considered in PFS analyses. In univariate analyses, we observed a negative impact of BIRC3 mutations and 11q22 deletion in both regimens, while the unmutated IGHV status was associated with a significantly shorter PFS only in the FCR-treated cohort. In a multivariate analysis, only deletion 11q22 in both regimens, and the unmutated IGHV in the FCR cohort maintained an independent association with the reduced PFS. Notably, sole 11q22 deletion, without an ATM mutation on the other allele, manifested the shortest PFS of all analyzed markers. Deletion 11q22 and IGHV status predict PFS in previously untreated CLL patients.
ER  -

ŠPUNAROVÁ, Michaela, Nikola TOM, Šárka PAVLOVÁ, Marek MRÁZ, Yvona BRYCHTOVÁ, Michael DOUBEK, Anna PANOVSKÁ, Hana SKUHROVÁ FRANCOVÁ, Anna BRZOBOHATÁ, Šárka POSPÍŠILOVÁ, Jiří MAYER and Martin TRBUŠEK. Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: Clinical practice experience (Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: clinical practice experience). \textit{Leukemia Research}. Oxford: PERGAMON-ELSEVIER SCIENCE LTD, 2019, vol.~81, JUN 2019, p.~75-81. ISSN~0145-2126. Available from: https://dx.doi.org/10.1016/j.leukres.2019.04.015.

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