Study Suggests a High Charlson Comorbidity Index Score Negatively Impacts OS, RS in CLL

When also considering age and Rai score, the effect of Charlson comorbidity index score on mortality was found to be statistically nonsignificant for patients with chronic lymphocytic leukemia, although higher scores were associated with worse overall and relative survival.

A study published in the International Journal of Environmental Research and Public Health revealed that among patients with chronic lymphocytic leukemia (CLL), a high Charlson comorbidity index (CCI) score negatively impacted overall survival (OS) and relative survival (RS).

However, when also considering age and Rai score, which indicates severity of CLL and comorbidities present at diagnosis, the effect of CCI score on mortality was found to be statistically nonsignificant for this patient population.

“These population-based data will provide insights into the relationship between comorbidities and CLL in a real-world setting,” wrote the study authors, who were led by Alicia Villavicencio.

Using the Girona Cancer Registry of Spain, the investigators extracted incident CLL cases diagnosed between 2008 and 2016. Of note, CLL and small lymphocytic lymphoma (SLL) cases were classified together in accordance with WHO recommendations, given that both share clinical and pathological features.

Data on Rai stage were retrospectively obtained from medical records. CCI score was also calculated for each patient based on the health conditions revealed to be present at the time of diagnosis. Based on CCI score, patients were classified into 5 groups, including absence of comorbidity (0), low risk (1–2), moderate risk (3), high risk (>4), and unknown CCI status.

Of a total of 400 cases with a median follow-up time of 5.2 years, the median age at diagnosis was 72 years (interquartile range, 60-80 years), 230 (57.5%) were men, and most (56.7%) had early-stage CLL (Rai stage 0) at diagnosis. As anticipated, patients with a higher CCI score were older and were more often diagnosed with advanced Rai stages; no differences were identified according to sex or period of diagnosis.

With the exception of 20 patients, 380 (99.5%) presented with at least 1 comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most commonly reported disease. Of the comorbid patients, CCI score was low in 86 (21.5%), moderate in 151 (37.7%), high in 118 (29.5%), and unknown in 25 (6.2%).

Overall, 5-year OS rates was 68.8% (95% CI, 64.4%-73.6%) and RS rate was 99.5% (95% CI, 93.6%-106.0%). However, survival estimates decreased substantially with increasing CCI scores, especially in individuals with 3 or more comorbidities.

Among a total of 168 patients who died during follow-up, the cause of death could be determined in 155 (92.2%) with 86 (55.5%) determined to be CLL-related. No statistically significant differences were reported according to CCI, age, sex, Rai score, or period of diagnosis.

On univariate analysis, a higher CCI score was associated with higher overall mortality (HR, 5.82; 95% CI, 1.44-23.49), though not with CLL-related (HR, 1.28; 95% CI, 0.17-9.18) or CLL-unrelated (HR, 2.83; 95% CI, 0.39-20.72) mortality. After adjusting for age, sex, Rai stage, and period of diagnosis on multivariate analysis, a higher CCI score was not associated with a higher overall mortality (HR, 2.05; 95% CI, 0.47-8.90) or CLL-related mortality (HR, 0.62; 95% CI, 0.07-5.30).

“However, our results must be interpreted with caution, since we might have been limited by sample size and, particularly, by death cause misclassification,” the authors noted. “We relied on official data on the basic cause of death—and not the secondary cause of death. Thus, we were unable to subclassify CLL-related mortality into more informative categories (e.g., disease progression, second primary cancer, infection, and other health conditions).”

“In CLL-related causes, we included all hematological malignancies, suspecting misclassifications of CLL cases and treatment-related diseases,” added the authors. “However, there might be some real secondary primary hematological malignancies that were wrongly located in CLL-related causes.”

Moving forward, the investigators suggested that further real-world data including clinical and treatment variables will be necessary to better understand the role of comorbidities on CLL outcomes, and to provide better-tailored prognostic tools for the comorbid and elderly populations.


Villavicencio A, Solans M, Zacarías-Pons L, et al. Comorbidities at diagnosis, survival, and cause of death in patients with chronic lymphocytic leukemia: a population-based study. Int J Environ Res Public Health. 2021;18(2):701. doi:10.3390/ijerph18020701