Augmented Berlin-Frankfurt-Muenster (ABFM) regimen for children with standard-risk acute lymphoblastic leukemia (SR-ALL) and slow early response (SER)

Abstract

9511 Background: Numerous studies have shown that SER in ALL has a negative impact on outcome. Children's Cancer Group CCG-1882 demonstrated that post-induction intensification greatly improved the outcome of children with high-risk ALL and SER. Five year event-free-survival (EFS), and overall survival (OS) for the augmented regimen was 75 ± 4% vs 55 ± 4.5%, and 78 ± 4% vs 67 ± 5% for the standard regimen, p <0.001 and 02 respectively (N Engl J Med 1998; 338:1663–71). Methods: Therefore, COG-1952 and COG- 1991, studies for patients with SR-ALL, assigned the slow early responders to augmented therapy, while others were randomized according to the study design. Study eligibility criteria were similar for both, and included newly diagnosed children with National Cancer Institute SR criteria. COG-1952 accrued a total of 2,027 patients and COG-1991 accrued 3,054. In COG-1952 patients were deemed SER if their day-7 marrow had >5% blasts, and their day-14 marrow >25%. COG-1991 used the same criteria for SER, but also added patients whose day-7 marrow had >25% blasts and their day-14 marrow had >5% blasts to the SER group. This was based on the unfavorable outcome of this subgroup in COG-1952. The augmented therapy in COG-1991 like the CCG-1882 and COG-1952, was based on a COG-modified ABFM, but differed in using dexamethasone as the sole steroid and pegylated asparaginase as the asparaginase preparation, as compared to prednisone in induction and maintenance, and native E coli asparaginase. Results: Comparative groups with days 7 and 14 M3 marrows and unfavorable cytogenetics included 126 patients from COG-1991 and 81 from the COG-1952 were assigned to their corresponding ABFM regimens. Four year EFS and OS were 85% ± 5% and 90 ± 4% for CCG-1991 vs 61 ± 5.6% and 75 ± 5% for CCG-1952, p = 0.003 and 0.04 respectively. Conclusion: We conclude that the use of dexamethasone, and pegylated asparaginase greatly improves the outcome of children with NCI-SR with SER treated on a modified augmented BFM therapy, thus supporting the use of these agents in ALL therapy. No significant financial relationships to disclose.