Relationship between co-morbidities at diagnosis, survival and ultimate cause of death in patients with chronic lymphocytic leukaemia (CLL): a prospective cohort study

Abstract

The ultimate cause of death for most patients with newly diagnosed chronic lymphocytic leukaemia (CLL) and its relationship to co-morbid health conditions is poorly defined. We conducted a prospective cohort study that systematically followed 1143 patients diagnosed with CLL between June 2002 and November 2014. Comorbid health conditions at the time of CLL diagnosis and their relationship to survival and cause of death were evaluated. Collectively, 1061 (93%) patients had at least one co-morbid health condition at the time of CLL diagnosis (median number 3). Despite this, 89% of patients had a low-intermediate Charlson Comorbidity Index score (CCI) at diagnosis. After a median follow-up of 6 years, 225 patients have died. Death was due to CLL progression in 85 (46%) patients, infection in 14 (8%) patients, other cancer in 35 (19%) patients and comorbid health conditions in 50 (27%) patients. Higher CCI score and a greater number of major comorbid health conditions at the time of CLL diagnosis was associated with shorter non-CLL specific survival, but not with shorter CLL-specific survival on multivariate analysis. In conclusion, CLL and CLL-related complications (infections and second cancers) are the overwhelming cause of death in patients with CLL, regardless of CCI score and number of comorbid health conditions at diagnosis.

Keywords: causes of death; chronic lymphocytic leukaemia; comorbidities.

Fig 1.

Baseline comorbid health conditions in 1143 CLL patients. DVT, deep venous thrombosis; PE, pulmonary embolism; STD, sexually transmitted disease. ‘Other cancers’ did not include non-melanoma skin cancers.

Fig 2.

Overall survival. (A) Overall survival by Charlson Comorbidity Index (CCI) score at the time of CLL diagnosis. (B) Overall survival by number of major comorbidities (CM) at time of CLL diagnosis. Events included all types of death, both CLL-related, non-CLL related, and of unknown cause.

Fig 3.

CLL-specific and non-CLL specific mortality. (A) CLL-specific-mortality by Charlson Comorbidity Index (CCI) score at time of CLL diagnosis. (B) CLL-specific-mortality by number of major comorbidities (CM) at time of CLL diagnosis. (C) Non-CLL specific mortality by Charlson Comorbidity Index score at time of CLL diagnosis. (D) Non-CLL specific mortality by number of major comorbidities at time of CLL diagnosis.