Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 20 1 2026 02 09 14 29 Padideh Oghab Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Ali Erfan Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mohadese Poorpoone Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mohammadsaleh Peikar Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2025 05 21 2025 09 14 Background: Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are rare blood cancers with poorer survival in adolescents and young adults (AYAs) than in children. Pediatric-inspired regimens like CALGB 10403 have improved outcomes in AYAs. This study evaluated the effectiveness, feasibility, and treatment-related toxicities of CALGB 10403 in AYAs with ALL/LBL treated at Seyed Al-Shohada Hospital, Isfahan, Iran, from December 2021 to May 2024 Materials and Methods: AYAs aged 17-39 with newly diagnosed ALL/LBL (excluding Burkitt, Ph+, and prior treatment) were included.  Baseline characteristics and outcomes of interest (induction response, event-free and overall survivals) were collected.  Induction response was assessed via bone marrow (ALL) or CT scan/biopsy (LBL). Minimal residual disease (MRD) was evaluated by flow cytometry. Treatment-related toxicities were monitored and graded per CTCAE criteria. The feasibility of implementing the CALGB 10403 protocol was evaluated by measuring treatment delays. Results: Seventeen AYA patients with newly diagnosed ALL/LBL (median age 21) were enrolled, mostly male (14/17). Fourteen had ALL, and three had LBL. Extramedullary involvement was seen in 29%, including lymphadenopathy, bulky mediastinal masses, and CNS involvement. Sixteen patients (94%) achieved remission, with no deaths during the induction course. One-year EFS and OS were 77% and 100%, respectively. Common toxicities included hyperbilirubinemia, elevated transaminases, and infections. Treatment delays, mainly from non-adherence, occurred in 53%. Eight patients achieved MRD negativity after Course I. Conclusion: This study provides insights into the first Iranian experience with the CALGB 10403 protocol for AYAs with ALL/LBL, a regimen that has demonstrated encouraging survival outcomes in U.S. trials. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/2458 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/2458/1116