External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation

Abstract

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores' limited discriminative capacity.

Graphical abstract

Figure 1.

Distribution of the individual scores across the population. (A-F) Median (IQR) and number of patients per grouped stratum are provided. Scores tend to have a left (ie, favorable) bias. (F) Outliers in the EASIx score are shown in the inset. The Comorbidity-EBMT score is shown in the supplemental Appendix (supplemental Figure 1), and the distribution of the rDRI is provided in Table 1.

Figure 2.

Kaplan-Meier plots depicting the outcome of OS in each of the studied scores. (A-H) Increasing strata generally reflect poorer outcome in each of the scores.

Figure 3.

AUC curve for each score at 100 days, 1 year, 2 years, and 3 years posttransplantation. AUCs for prediction of OS (A), NRM (B), and relapse (C) are depicted.