Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation

Abstract

Purpose: Age has long been used as a major factor for assessing suitability for allogeneic hematopoietic cell transplantation (HCT). The HCT-comorbidity index (HCT-CI) was developed as a measure of health status to predict mortality risk after HCT. Whether age, comorbidities, or both should guide decision making for HCT is unknown.

Patients and methods: Data from 3,033 consecutive recipients of HLA-matched grafts from five institutions contributed to this analysis. Patients were randomly divided into a training set to develop weights for age intervals and a validation set to assess the performance of prognostic models.

Results: In the training set, patients age 20 to 39 years, 40 to 49 years, 50 to 59 years, and ≥ 60 years had hazard ratios for nonrelapse mortality (NRM) of 1.21 (P = .29), 1.48 (P = .04), 1.75 (P = .004), and 1.84 (P = .005), respectively, compared with those age younger than 20 years. Consequently, age ≥ 40 years was assigned a weight of 1 to be added to the HCT-CI to constitute a composite comorbidity/age index. In the validation set, the composite comorbidity/age score had statistically significantly higher c-statistic estimates for prediction of NRM (0.664 v 0.556; P < .001) and survival (0.682 v 0.560; P < .001) compared with age, respectively. Patients with comorbidity/age scores of 0 to 2 had comparable mortality risks regardless of conditioning regimens. Patients with scores of 3 to 4 and ≥ 5 had statistically significant higher mortality risks after high-dose versus nonmyeloablative regimens.

Conclusion: Age is a poor prognostic factor. The proposed composite measure allows integration of both comorbidities and age into clinical decision making and comparative-effectiveness research of HCT.

Fig 1.

Illustration of the relationship between age in years and the hazard ratio for nonrelapse mortality (NRM). Patients in the training group were sorted by age and divided into groups of 100 patients each. The dots represent the estimated hazard ratios for the association between each age group and NRM relative to a reference group (median age, 45 years; range, 42-49 years) using Cox regression models. A smooth curve fitted to the dots was generated to represent the relationship of age in years with NRM both before (black) and after (blue) adjustment for all other risk factors in the Cox regression model.

Fig 2.

Comparisons of outcome stratifications by the hematopoietic cell transplantation–comorbidity index (HCT-CI) and the composite comorbidity/age index (HCT-CI/age). (A, B) Cumulative incidences of nonrelapse mortality and (C, D) Kaplan-Meier estimates of overall survival among patients of the validation set (n = 1,180) as stratified by (A, C) the HCT-CI and (B, D) the composite comorbidity/age index.