Multivariate risk classification of patients with aggressive and indolent ATL. (A) Cox proportional hazards model identifying independent significant risk factors for OS in 152 aggressive (left) or 74 indolent ATL (right) cases. The final Cox model resulted from a backward elimination process that considered genetic alterations having a univariate Cox P value < .10 and clinical factors (age, JCOG-PI, and treatment content in aggressive ATL, or age and subtype in indolent ATL). (B) Distribution of risk factors showing overlap between patients with JCOG-PI high-risk, older age, PRKCB mutations, and PD-L1 amplifications in aggressive ATL (top) or those with IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions in indolent ATL (bottom). Patients who died within 1 year in aggressive ATL and within 3 years in indolent ATL are also shown. (C) Kaplan-Meier survival curves of 152 aggressive ATL cases and those categorized as JCOG-PI moderate-risk (n = 84) and high-risk (n = 68), stratified by the number of risk factors (older age, PRKCB mutations, and PD-L1 amplifications). (D) Kaplan-Meier survival curves of 74 indolent (chronic and smoldering), 40 unfavorable chronic, and 19 favorable chronic ATL cases, stratified by the presence of risk factors (IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions). The chronic subtype was classified into unfavorable and favorable subtypes based on the presence of clinical prognostic factors (low albumin, high BUN, and high LDH levels). The prognostic impact on OS was evaluated by log-rank test. CI, confidence interval.