Large B-cell lymphoma with IRF4-rearrangement (LBCL-IRF4+) among children, adolescents and young adults (CAYA), a narrative review

Abstract

Outcomes for pediatric non-Hodgkin lymphoma (NHL) have improved markedly over the past decade; however, reducing therapy-related toxicity while maintaining excellent survival remains a major challenge. This narrative review, conducted using a PCC (Population–Concept–Context) framework, summarizes current evidence on large B-cell lymphoma with IRF4-rearrangement (LBCL-IRF4⁺) in children, adolescents, and young adults (CAYA) below 30 years of age. Focusing on clinical presentation, pathological and molecular features, treatment strategies, and outcomes, based on literature searches in PubMed, Embase, and Web of Science performed in November 2025. LBCL-IRF4⁺ is a rare subtype, and evidence among these age groups is largely derived from small retrospective series. Available data indicate that patients with low-stage disease and/or follicular growth patterns may be candidates for treatment de-escalation, while those with advanced-stage or atypical presentations should be evaluated for underlying immunologic predispositions. This review underscores the importance of including LBCL-IRF4⁺ in future clinical trials to optimize therapy intensity and explore opportunities for safe de-escalation in selected patient groups.