A robust and validated integrated prognostic index for de fi ning risk groups in adult acute lymphoblastic leukemia: an EWALL collaborative study

Risk strati fication is crucial to the successful treatment of acute lymphoblastic leukemia (ALL). Although numerous risk factors have been identi fied, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from 4 contemporary academic national clinical trials, UKALL14, NILG-ALL10/07, GIMEMALAL1913, and PETHEMA-ALL-HR2011, to generate and validate the European Working Group for Adult ALL prognostic index (EWALL-PI), which is based on white blood cell count, genetics, and end of induction minimal residual disease (MRD). Individual patient risk scores were calculated for 778 patients aged 15 to 67 years in complete remission using the validated UKALL-PI formula, applying minor modi fications to re flect differences between pediatric 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 similar to 30% with no evidence of heterogeneity across trials or patient subgroups. EWALL-PI -de fined risk models outperformed the strati fication algorithms used by each trial. Threshold analysis revealed an EWALL-PI threshold that divided patients with B cell and T cell into standard (EWALL-PI <2.50) and high (EWALL-PI >= 2.50) risk groups, respectively. Per -trial analysis showed that patients at high risk had a signi ficantly increased relapse rate and inferior survival compared with patients with standard risk (subdistribution hazard ratio for relapse, ranged from 1.85 to 3.28; hazard ratio for death, 1.73 to 3.03). Subgroup analysis con firmed the robustness of these risk groups by sex, age, white blood cell count, and lineage. In conclusion, we validated an integrated risk model across 4 independent adult ALL clinical trials, demonstrating its utility de fining clinically relevant risk groups.