Value of Different Comorbidity Indices for Predicting Outcome in Patients with Acute Myeloid Leukemia

Abstract

Age is a dominant predictor of outcome in acute myeloid leukemia (AML). However, it is not clear to which extent comorbidities contribute to this effect. The objective of this study was to determine the impact of pretreatment comorbidities on survival of AML patients. In a single-center retrospective study 194 adult AML patients were included. The Hematopoietic cell transplantation comorbidity index (HCT-CI), the Adult Comorbidity Evaluation-27 (ACE-27) score and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) as well as data on demographics, cytogenetics, treatment and outcome were evaluated at the time of initial diagnosis by univariate and multivariate analysis. The study included 102 male and 92 female (median age 60.9 years) of which 173 (89.2%) received intensive chemotherapy. Median overall survival (OS) was 17 months. In univariate analysis, cardiovascular disease (26 vs 12 months, p = .005), severe hepatic disease (19 vs 4 months, p = .013) and renal impairment (17 vs 7 months, p = .016) was associated with inferior OS. For each index, the highest comorbidity burden was associated with reduced OS. However, in multivariate analysis only the ACE-27 score was associated with outcome. Besides ECOG ≥ 2 and poor cytogenetics only the ACE-27 score but not higher age was associated with OS in the group of patients receiving intensive therapy. Adjusted hazard ratios were 3.1, 3.5 and 4.0 for mild, moderate and severe ACE-27-assessed comorbidities, respectively (p = .012). Our study confirms that comorbidities significantly impact survival of AML patients and a pretreatment assessment of comorbidities may help to identify patients with poor outcome.

Fig 1. Distribution of individual comorbidities.

Individual comorbidities among 194 AML patients as assessed by the three indices, respectively. Hepatic diseases are not assessed by the ACE-27 score, and infections are only assessed by the HCT-CI.

Fig 2. Survival curves according to the 3 comorbidity indices HCT-CI, ACE-27 and CIRS-G.

Risk groups based on comorbidity were stratified by HCT-CI, ACE-27 score and CIRS-G in all 194 patients and differences in survival between groups were tested using the long-rank test.

Fig 3. Overall survival for the entire patient cohort and for different treatment strategies.

Kaplan-Meier analysis was performed and the effect of treatment on OS was tested using the long-rank test. (A) OS in the entire patient cohort. The median OS was 17 months. (B) OS in the patient groups according to treatment strategy. The median OS of the 173 patients treated intensively was 18 months (blue line) while the 21 patients who received palliative treatment, had a median OS of one month (green line).

Fig 4. Distribution of ACE-27 categories in different age groups.

Distribution of ACE-27 score of none, mild, moderate and severe comorbidities among four age groups in all 194 AML patients. 22 patients were younger than 41 years, 53 patients were between 41 and 59 years old, 119 patients were more than 60 and 58 patients more than 70 years old. Increasing age was significantly associated with higher ACE-27 score as analyzed by x² test (p < .000).