Introduction T‐cell acute lymphoblastic leukemia (T‐ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre‐B ALL. We aimed to decrease T‐ALL relapses by intensifying our regimen. Methods Patients with T‐ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Reintensification. Cranial radiation was limited to patients with WBC ≥ 100 k/μl at diagnosis and/or patients with CNS2/CNS3 status. Results Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed up for a median of 70 months (range 14–181). Median age at diagnosis was 9 years (range 0.5–17.8). Forty‐eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range 14–74). The 5‐year‐EFS estimates for patients who received the augmented regimen versus standard regimen were 87% ± 4.9% versus 67% ± 6.8% (p = .03); and the 5‐year‐OS estimates were 87% ± 5.1% versus 71% ± 6.3% (p = .06), respectively. Treatment related mortality (TRM) was reported in two patients treated per standard regimen but none for patients who received the augmented regimen. Conclusions We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total‐XV regimen for patients with T‐ALL that resulted in improved outcome with no treatment related mortality.
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