Detailed Information on Publication Record
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:
Impact factor
Impact factor: 2.214
RIV identification code
RIV/00216224:14110/19:00108468
Organization unit
Faculty of Medicine
UT WoS
000468184500012
Keywords in English
CLL; chemoimmunotherapy; deletion 11q22; IGHV; BIRC3; ATM
Tags
International impact, Reviewed
Změněno: 27/5/2020 13:41, Mgr. Tereza Miškechová
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 |
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