Pediatric patients with acute lymphoblastic leukemia (ALL) achieve considerably higher disease-free survival (DFS) rates with current chemotherapy regimens than adults with ALL. Young adults have been shown to achieve superior survival outcomes when treated with native E coli asparaginase-based regimen.1 The DFCI Adult ALL Consortium Phase 2 Trial was conducted to evaluate the feasibility of a pegylated-asparaginase (peg-asp) pediatric regimen during the induction and consolidation phase (every 2 weeks for 15 doses); the results of which were reported by DeAngelo and colleagues.2 Of the 110 eligible patients, the first 65 patients were treated with the initial study design of intravenous peg-asp (2500 IU/m2 every 2 weeks) during induction and peg-asp every 2 weeks for 15 doses during consolidation; however, the subsequent 45 patients were treated on a modified schedule following the high incidence of asparaginase toxicities (mainly hyperbilirubinemia), in which peg-asp during induction was replaced with native E coli asp (25,000 IU/m2 intramuscularly) and peg-asp during the consolidation phase was delivered at a decreased dose of 2000 IU/m2 every 3 weeks for 10 doses. Using the peg-asp regimen, the complete response (CR) rate overall after 4 weeks was 89%; CR rate was 87% with the decreased dose. At a median follow-up of 42.2 months, the estimated 3-year DFS was 73% in patients who achieved CR; the estimated 3-year overall survival (OS) was 75%. Subgroup analysis showed that higher body mass index minimal residual disease >10-4 was associated with lower OS benefit. Overall, grade ?3 adverse events included pancreatitis, hypersensitivity, thrombosis, elevations in aspartate transaminase, alanine transaminase, and bilirubin, hemorrhage, and neutropenic infection. Overall, 2 deaths were reported during induction therapy due to sepsis and central nervous system hemorrhage. Based on these results, the authors concluded that the administration of a peg-asp–based dose-intensified pediatric regimen to adults with ALL is feasible albeit at a lower dose and less frequent schedule.
