Survival outcomes of adolescents and young adults with lymphoblastic lymphoma treated with pediatric-inspired protocols in the Middle East

Abstract Lymphoblastic lymphoma (LBL) is a highly aggressive neoplasm of precursor lymphoid cells, accounting for approximately 2% of all non-Hodgkin lymphomas. Most cases (~90%) are of T-cell origin, with the remainder being B-cell. Due to its rarity, particularly in adolescents and young adults (AYA), data on treatment outcomes in this population are limited—especially in the Middle East. We conducted a retrospective analysis of 20 AYA patients (aged 14–44 years) diagnosed with LBL between 2015 and 2025 at King Faisal Specialist Hospital center, Saudi Arabia. Diagnoses were made according to the 2022 WHO classification. Clinical features, treatment-related toxicities, and survival outcomes were analyzed. The cohort had a median age of 24 years and was predominantly male (70%). T-cell LBL comprised 85% of cases. Mediastinal involvement was present in 85%, bulky disease in 65%, and CNS involvement in 10%. All patients received pediatric-inspired AYA protocols. The overall response rate was 85%. At last follow-up, 70% of patients were alive. Disease relapse or progression occurred in 25%, with 80% of these patients still alive. The 5-year overall survival (OS) was 65.5%, with no statistically significant difference between T-cell and B-cell LBL (P = .09). Patients who achieved complete or partial remission had improved OS, though this did not reach statistical significance (P = .06). The 5-year progression-free survival (PFS) was 70.2%. Six patients underwent hematopoietic stem cell transplantation (HSCT), with four (66.7%) surviving at last follow-up. Asparaginase-related toxicities included thrombosis (30%) and hemorrhage (15%). This study provides one of the first reports on outcomes of AYA patients with LBL in the Middle East. Despite the aggressive nature of the disease, pediatric-inspired AYA protocols yield encouraging survival outcomes. Early post-transplant survival appears promising. Larger prospective studies are needed to validate these findings and optimize treatment strategies, particularly regarding the role of HSCT.