Comparison of Conventional Chemotherapy Regimens in Adults With Acute Lymphoblastic Leukemia: A Systematic Review and Pooled Survival Analysis

OBJECTIVES: Acute lymphoblastic leukemia (ALL) primarily affects children, with an incidence rate of 75%. Despite significant progress in pediatric ALL chemotherapy, treatment outcomes in adults remain unsatisfactory, with overall survival (OS) rates between 30% and 40%. Notably, there is no clear evidence indicating which chemotherapy regimen is optimal for treatment-naive ALL patients. This study aims to identify which frontline chemotherapy regimen provides the best response in ALL patients.

METHODS: This systematic review and pooled survival analysis examined survival outcomes in patients with B-cell or T-cell Philadelphia chromosome-negative (Ph-) ALL treated with conventional chemotherapy regimens. Clinical trials and randomized controlled trials that had been published between the inception of the database and May 10, 2024, were included. Methodological quality was assessed using the Downs and Black checklist and the revised Cochrane risk-of-bias tool. Kaplan-Meier curves for OS, event-free survival (EFS), and disease-free survival (DFS) were extracted and reconstructed for pooled survival analysis by chemotherapy regimens.

RESULTS: Seven studies met the inclusion criteria, comprising one randomized controlled trial and six clinical trials. Five chemotherapy regimens were identified: CALGB 10403, CALGB 8811, Hyper-CVAD, GRAALL 2005, and GRAALL-2003, with complete remission rates of 89%, 85%, 92%, 92%, and 93%, respectively. CALGB 10403 demonstrated the best OS with a five-year survival rate of 63.2% (95% confidence interval [CI], 69.7% to 57.2%). CALGB 8811 showed the best EFS and DFS for follow-ups under four years, with a 58.5% survival rate (95% CI, 47.6% to 71.8%), while CALGB 10403 and GRAALL 2005 had better outcomes for over four years.

CONCLUSIONS: The comprehensive synthesis shows that the CALGB 10403 regimen has the best overall survival rate and superior long-term disease-free rate. If patients do not experience serious side effects, CALGB 10403 can be recommended for long-term treatment for adults with ALL.