The chronic lymphocytic leukemia comorbidity index (CLL-CI): a three-factor comorbidity model.

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Clinical cancer research : an official journal of the American Association for Cancer Research


washington; seattle; swedish cancer


PURPOSE: Comorbid medical conditions define a subset of chronic lymphocytic leukemia (CLL) patients with poor outcomes. However, which comorbidities are most predictive remains understudied.

EXPERIMENTAL DESIGN: We conducted a retrospective analysis from 10 academic centers to ascertain the relative importance of comorbidities assessed by the Cumulative Illness Rating Scale (CIRS). The influence of specific comorbidities on event-free survival (EFS) was assessed in this derivation dataset using random survival forests to construct a CLL-specific comorbidity index (CLL-CI). Cox models were then fit to this dataset and to a single-center, independent validation dataset.

RESULTS: The derivation and validation sets comprised 570 patients (59% receiving Bruton tyrosine kinase inhibitor [BTKi]) and 167 patients (50% receiving BTKi), respectively. Of the 14 CIRS organ systems, three had a strong and stable influence on EFS: any vascular, moderate/severe endocrine, moderate/severe upper gastrointestinal comorbidity. These were combined to create the CLL-CI score, which was categorized into 3 risk groups. In the derivation dataset, the median EFS was 58, 33, and 20 months in the low, intermediate, and high risk groups, correspondingly. Two-year overall survival (OS) rates were 96%, 91%, and 82%. In the validation dataset, median EFS was 81, 40, and 23 months (two-year OS rates 97%/92%/88%), correspondingly. Adjusting for prognostic factors, CLL-CI was significantly associated with EFS in patients treated with either chemo-immunotherapy or with BTKi in each of our 2 datasets.

CONCLUSIONS: The CLL-CI is a simplified, CLL-specific comorbidity index which can be easily applied in clinical practice and correlates with survival in CLL.

Clinical Institute