Examining the Usefulness of the Charlson Comorbidity Index to Predict Early Mortality in Patients with Acute Myeloid Leukaemia
Authors: Bakri Mohamed Mohamed , Millar Seán R , Mykytiv Vitaliy , McMorrow Rose , Donnelly Conan , Walsh Paul M , O'Leary Eamonn , Orfali Nina , Murphy Philip , Browne Paul V. , Quinn John , O'Gorman Peter , Clifford Ruth , El Hassadi Ezzat , Gilligan Oonagh , Krawczyk Janusz , O'Dwyer Michael E. , Szegezdi Eva , Cahill Mary R 
Published: November 2021

Abstract
Background and aims: Acute myeloid leukaemia (AML) is a relatively rare haematological malignancy which is the most common acute leukaemia in adults. Patients with AML often have a substantial comorbidity burden. Consequently, different scores are used in clinical practice to predict outcomes in patients with multiple comorbidities. The Charlson Comorbidity Index (CCI), calculated based on 19 different medical conditions, weighs the comorbidities to measure a patient's burden of disease. Previous publications have suggested that the CCI may be useful in determining survival in AML patients. However, the CCI is not in routine use in Ireland for assessing patients with AML. In this study we examined the usefulness of the CCI to predict early mortality in AML patients, drawing on data from the Extended Blood Cancer Registration (EBCR) in Ireland.
Methods: The EBCR was undertaken by National Cancer Registry Ireland registrars trained by consultant haematologists and deployed in national centres. Data collection began in 2017 and continued to 2019; 141 AML patients underwent extended data registration. Comorbidities were identified by ICD-9 codes and chart review. Kaplan Meier curves and Cox regression analyses were used to determine the usefulness of the CCI to predict early mortality in AML patients.
Results: Of the 141 AML patients, 82% were between 50 and 70 years of age and 84 had died by 31/12/2019 (median survival time = 289.0 days). The median survival time for patients in the lowest tertile of the CCI was 498.5 days, compared to 246.0 and 116.5 days for subjects in tertiles 2 and 3, respectively (Figure 1. Log rank P-value &lt;.001). In Cox regression analysis, a dose-response relationship was observed, with patients in the highest CCI tertile displaying a greater risk (HR = 4.90, 95% CI: 2.79-8.63) of mortality compared to subjects in tertile 2 (HR = 2.74, 95% CI: 1.64-4.57) and tertile 1 (reference). However, this relationship was attenuated, and non-significant, in analyses which adjusted for age at diagnosis and in a further multivariable model.
Conclusions: Although results demonstrate a strong relationship between the CCI and early mortality in AML patients, our findings suggest that the CCI provides little or no additional prognostic information beyond that which is obtained from age at AML diagnosis alone. This study highlights the importance of validating risk assessment tools in order to determine their potential usefulness in a clinical setting and emphasise the importance of weighing in the treatment decision making paradigm.
The Blood Cancer Network Ireland (BCNI) thank the Science Foundation of Ireland (SFI) and the Irish Cancer Society (ICS) for funding (2015-2021).
We also thank our colleagues in the National Cancer Registry Ireland for assistance, advice and guidance.
Figure 1 Figure 1.

Disclosures
Quinn: Takeda: Honoraria. O'Dwyer: Bristol Myers Squibb: Research Funding; Janssen: Consultancy; ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Szegezdi: ONK Therapeutics: Research Funding.