Abstract
Introduction: Chronic lymphocytic leukemia (CLL) is a disease with an extremely variable clinical course. Biological features of CLL with impact on prognosis have been well defined over the last decades, but there is little data on how comorbidities of CLL patients (pts) may influence overall survival. Importantly, most of the studies on this topic included selected patient populations from secondary or tertiary centers with significant bias caused by high proportion of referred patients with unfavourable disease course.
Aims: to evaluate impact of major comorbidities on overall survival (OS) in an unselected CLL population.
Patients and methods: We performed a retrospective analysis of 202 pts (median age, 69 years, 60% males), who were diagnosed with CLL according to NCI-WG and IWCLL criteria in the Hradec Králové district (population 162,820 as of December 2011) between January 1st, from 1999, and December 31st, 2013. Influence of four major comorbidities (ischemic heart disease [IHD], diabetes mellitus [DM] on therapy, chronic obstructive pulmonary disease [COPD] and second primary malignancy [SPM]) as well as number of concomitant medications as an indicator of total comorbidity burden were evaluated using Kaplan-Meier curves and log-rank test: Multivariate analysis was performed using the Enter method
Results: Basic characteristics are listed in Table 1. A total of 37 pts (18%) had IHD, 30 (15%) had DM, 18 (9%) had COPD and 26 (13%) had SPM. Only IHD had major impact on OS (p=0.0005, Fig.1) in univariate analysis. Using receiver operator curve (ROC) analysis, it was determined that the optimal cut-off associated with shorter OS was ≥ 4 concomitant medications (p=0.029, Fig.2). Cox regression analysis included the following variables which proved significant in univariate analysis: Rai modified risk, age, IHD, number of concomitant medications, and year of diagnosis (1999-2005 vs. 2006-2013). High or intermediate modified Rai risk (p<0.0001), age ≥ 70 (p<0.0001), year of diagnosis 2006-2013 (p= p<0.0001) were significant predictors of shorter OS and there was a trend towards for pts IHD (p= 0.059) in multivariate analysis, the cumulative number of the 4 major comorbidities did not have statistically significant impact on OS.
Conclusion: Our results indicate that ischemic heart disease and number of concomitant medications are significantly associated with shorter overall survival in patients with CLL. Supported by program PROGRES Q40/08 and by DRO (UHHK, 00179906) from Ministry of Health, Czech Republic.
Vodarek: Janssen: Consultancy, Honoraria, Other: Travel grants ; Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants ; Servier: Consultancy, Honoraria, Other: Travel grants . Simkovic: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Motyckova: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding, Speakers Bureau. Belada: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Smolej: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau.
