A robust and validated integrated prognostic index for defining risk groups in adult ALL: A EWALL collaborative study.

Abstract

Risk stratification is crucial to the successful treatment of ALL. Although numerous risk factors have been identified, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from four contemporary academic national clinical trials: UKALL14, NILG-ALL10/07, GIMEMA-LAL1913, PETHEMA-ALL-HR2011 to generate and validate the EWALL prognostic index (EWALL-PI) which is based on white blood cell count, genetics, and end of induction minimal residual disease. Individual patient risk scores were calculated for 778 patients in complete remission aged 15-67 years old using the validated UKALL-PI formula; applying minor modifications to reflect differences between paediatric and adult ALL. Per-trial analysis revealed that EWALL-PI correlated with relapse and death. Regression analysis revealed that each unit increase in EWALL-PI increased the risk of relapse or death by ~30% with no evidence of heterogeneity across trials or patient subgroups. EWALL-PI-defined risk models outperformed the stratification algorithms used by each trial. Threshold analysis revealed an EWALL-PI threshold that divided B and T-cell patients into standard (EWALL-PI <2·50) and high (EWALL-PI ≥2·50) risk groups. Per-trial analysis showed that high-risk patients had a significantly increased relapse rate and inferior survival compared with standard-risk patients (subdistribution hazard ratio ranged from 1.85 to 3.28 for relapse and hazard ratio 1.73 to 3.03 for death). Subgroup analysis confirmed the robustness of these risk groups by sex, age, white cell count and lineage. In conclusion, we validated an integrated risk model across four independent adult ALL clinical trials demonstrating its utility defining clinically relevant risk groups.