Anaplastic Large Cell Lymphoma in Children: 20-year Immune-Oriented Treatment Experience

Background: Anaplastic large cell lymphoma (ALCL) accounts for up to 15% of all pe-diatric and adolescent non-Hodgkin lymphomas and is characterized by significant clinical, morphological, and immunohistochemical heterogeneity. Expression of T-cell markers on tumor cells is considered as one of the factors of an unfavorable prognosis in ALCL. However, no treatment protocols based on the ALCL immunological heterogeneity have been used, yet. Objective: To compare the effectiveness of immunophenotype–oriented chemotherapy in children with ALCL treated according to the ALCL NII DOiG 2003 protocol versus the standard NHL-BFM 95 protocol. Methods: A retrospective-prospective analysis of 100 newly diagnosed ALCL patients, who were treated between 2000 and 2023, was performed across five pediatric oncology and hematology centers in Russia. Patients were divided into two groups: those treated with the NHL-BFM 95 protocol (n=52) and those treated with the ALCL NII DOiG 2003 protocol (n=48). Comparative analysis used Kaplan-Meier survival curves constructed for each group, and statistical analysis was performed with IBM SPSS Statistics 21.0. Results: The 10-year overall survival was significantly higher in the ALCL NII DOiG 2003 group (95.3% ±3.3%) compared to that of the NHL-BFM 95 group (82.0% ±5.4%, p=0.037). Event-free survival was also improved (95.3% ±3.3% vs. 68.6% ±6.5%, p=0.001), as well as the relapse-free survival (97.3% ±2.7% vs. 74.4% ±6.4%, p=0.003). Conclusions: The immunophenotype-oriented approach of the ALCL NII DOiG 2003 protocol provides significantly improved long-term outcomes than the common NHL-BFM 95. These findings support the benefit of the personalized immunologically targeted therapy in pediatric ALCL treatment.