Sixteen Years' Experience in Treating Adolescents and Young Adult (AYA) with Philadelphia-Negative Acute Lymphoblastic Leukemia (Ph- ALL) with a Modified Pediatric ALL Protocol

Introduction Several studies have shown superior outcomes of AYA with Ph- ALL when a pediatric or a pediatric-inspired ALL protocol is utilized. Since 2003, we have been using a modified pediatric ALL protocol in our Ph- AYA ALL patients, aiming to improve their outcomes. Methods This retrospective study evaluated 95 consecutive AYA Ph- ALL patients aged 14–39 years treated at our center with our modified ALL protocol from January 2003 to December 2019. The protocol is a modified CCG/COG protocol that consists of a 4-drug induction followed by 8 weeks of augmented consolidation. This is followed by the first interim maintenance (IM-1) with high-dose methotrexate (HD-MTX), delayed intensification (DI), a second IM (IM-2) with Capizzi MTX, and then 2 years of maintenance therapy for females and 3 years for males. Since July 2016, we have amended the protocol to include rituximab in all Precursor-B cell ALL (re-B ALL) patients. In October 2018, we have added blinatumomab for post-consolidation MRD-positive Pre-B ALL patients. Results Median age was 17 years, with 45% of the patients 18 years and older. The male-to-female ratio was 1.6, 75.8% had Pre-B phenotype, and 24.2% had T-cell ALL. CR rate was 94.7% with 5 (5.3%) induction failures and 3 (3.2%) induction deaths. End-of-induction MRD evaluation was available in 86 patients; of those, 72% achieved MRD negativity. After a median follow-up time of 58.8 months, the 5-year OS was 80%, and the 5-year EFS was 65%. The cumulative incidence of relapse was 22.1%. None of the baseline characteristics (age, gender, phenotype, or WBC count) have impacted the OS in uni/multivariate analysis. With regards to treatment-related toxicities, venous thromboembolism (VTE) occurred in 16.8%. Additionally, symptomatic avascular necrosis (AVN) developed in 13.7%, peripheral neuropathy of grade III or IV severity in 14.7%, and pancreatitis in 4.2%. Conclusion Utilizing a pediatric ALL protocol by adult hematologists is feasible and leads to superior outcomes compared to historical adult ALL protocol results. The 5-year EFS and OS in our cohort are promising. AVN and VTE occurred in more than 10% of the patients. More work is certainly needed to further improve outcomes and decrease toxicities.