A Modified CALGB 10403 in Adolescents and Young Adults with Acute Lymphoblastic Leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMIC) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included use of E. coli asparaginase, 6-mercaptopurine instead of thioguanine and use of rituximab among CD20 positive patients. A total of 95 patients with a median age of 23 years (range 14-49) treated with this modified scheme were prospectively assessed at five centers in Mexico and one in Guatemala. Among these, 87.8% achieved a complete response following induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (HR: 4.28 [95%CI: 1.81-10.10]) and post-induction Minimal Residual Disease (MRD) (HR: 4.67 [95%CI: 1.75-12.44]). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation), and treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.