Improving risk-stratification of patients with chronic lymphocytic leukemia using multivariate patient similarity networks.
Adult
Aged
Aged, 80 and over
Cluster Analysis
Cohort Studies
DNA Mutational Analysis
Decision Trees
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ diagnosis
Male
Middle Aged
Multivariate Analysis
Neural Networks, Computer
Precision Medicine
/ methods
Predictive Value of Tests
Prognosis
Risk Assessment
CLL
Multivariate and network-based approaches
Precision medicine
Prognostication
Risk patient subsets
Journal
Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
24
09
2018
revised:
04
02
2019
accepted:
18
02
2019
pubmed:
11
3
2019
medline:
18
12
2019
entrez:
11
3
2019
Statut:
ppublish
Résumé
Better risk-stratification of patients with chronic lymphocytic leukemia (CLL) and identification of subsets of ultra-high-risk (HR)-CLL patients are crucial in the contemporary era of an expanded therapeutic armamentarium for CLL. A multivariate patient similarity network and clustering was applied to assess the prognostic values of routine genetic, laboratory, and clinical factors and to identify subsets of ultra-HR-CLL patients. The study cohort consisted of 116 HR-CLL patients (F/M 36/80, median age 63 yrs) carrying del(11q), del(17p)/TP53 mutations and/or complex karyotype (CK) at the time of diagnosis. Three major subsets based on the presence of key prognostic variables as genetic aberrations, bulky lymphadenopathy, splenomegaly, and gender: profile (P)-I (n = 34, men/women with CK + no del(17p)/TP53 mutations), P-II (n = 47, predominantly men with del(11q) + no CK + no del(17p)/TP53 mutations), and P-III (n = 35, men/women with del(17p)/TP53 mutations, with/without del(11q) and CK) were revealed. Subanalysis of major subsets identified three ultra-HR-CLL groups: men with TP53 disruption with/without CK, women with TP53 disruption with CK and men/women with CK + del(11q) with poor short-term outcomes (25% deaths/12 mo). Besides confirming the combinations of known risk-factors, the used patient similarity network added further refinement of subsets of HR-CLL patients who may profit from different targeted drugs. This study showed for the first time in hemato-oncology the usefulness of the multivariate patient similarity networks for stratification of HR-CLL patients. This approach shows the potential for clinical implementation of precision medicine, which is especially important in view of an armamentarium of novel targeted drugs.
Sections du résumé
BACKGROUND
Better risk-stratification of patients with chronic lymphocytic leukemia (CLL) and identification of subsets of ultra-high-risk (HR)-CLL patients are crucial in the contemporary era of an expanded therapeutic armamentarium for CLL.
METHODS
A multivariate patient similarity network and clustering was applied to assess the prognostic values of routine genetic, laboratory, and clinical factors and to identify subsets of ultra-HR-CLL patients. The study cohort consisted of 116 HR-CLL patients (F/M 36/80, median age 63 yrs) carrying del(11q), del(17p)/TP53 mutations and/or complex karyotype (CK) at the time of diagnosis.
RESULTS
Three major subsets based on the presence of key prognostic variables as genetic aberrations, bulky lymphadenopathy, splenomegaly, and gender: profile (P)-I (n = 34, men/women with CK + no del(17p)/TP53 mutations), P-II (n = 47, predominantly men with del(11q) + no CK + no del(17p)/TP53 mutations), and P-III (n = 35, men/women with del(17p)/TP53 mutations, with/without del(11q) and CK) were revealed. Subanalysis of major subsets identified three ultra-HR-CLL groups: men with TP53 disruption with/without CK, women with TP53 disruption with CK and men/women with CK + del(11q) with poor short-term outcomes (25% deaths/12 mo). Besides confirming the combinations of known risk-factors, the used patient similarity network added further refinement of subsets of HR-CLL patients who may profit from different targeted drugs.
CONCLUSIONS
This study showed for the first time in hemato-oncology the usefulness of the multivariate patient similarity networks for stratification of HR-CLL patients. This approach shows the potential for clinical implementation of precision medicine, which is especially important in view of an armamentarium of novel targeted drugs.
Identifiants
pubmed: 30852300
pii: S0145-2126(19)30031-1
doi: 10.1016/j.leukres.2019.02.005
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
60-68Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.