Adolescent and Young Adult Patients Treated with Modified Augmented Berlin-Frankfurt-Muenster Therapy

Abstract 3250

Pediatric protocols for acute lymphoblastic leukemia (ALL) are currently employed by many groups to treat adolescents and young adults (AYA) with ALL. Adults up to age 55 are presently enrolled in such treatment regimens, and investigators have reported excellent results in these young adult patients (pts). Augmented Berlin-Frankfurt-Muenster therapy has been shown to be effective therapy for adolescents with ALL. To evaluate the efficacy and toxicity of this therapy in young adults, we designed a protocol of modified augmented Berlin-Frankfurt-Muenster (ABFM) therapy for patients with ALL from age 12 to 40. 70 pts have been enrolled on protocol and are evaluable for toxicity. 60 pts with de novo Philadelphia chromosome negative ALL have completed at least 29 days of therapy (induction) on protocol. They have the following characteristics: 52 (87%) pts have pre-B ALL and 8 (13%) have T-ALL. The median age is 20 (mean=22; range=13-39). The median presenting WBC=5.2 (mean=32; range= 0.4–494). 58/60 (97%) pts have achieved a remission. There have been no induction deaths. 49(82%) pts have attained remission by 15 days of induction, while 11 (18%) have been slow responders. 5/60 (8%) pts have required an extension of induction by 2 weeks. At day 29 of therapy, 38 (63%) pts had negative minimal residual disease (MRD) by flow cytometry, 15 (25%) patients were positive for MRD, 7 were suspicious or not available. By day 84 of therapy, 46 (77%) pts were negative for MRD and 9 (15%) were positive. Currently, there have been 10 relapses and 9 deaths. Toxicities in the entire group include severe asparaginase allergy in 15 (21%) pts, thrombus formation in 15 (21%) pts, hyperbilirubinemia grade III-IV in 19 (27%) pts, ALT/AST grade III-IV in 20 (28%) pts, CNS stroke-like symptoms in 6 (8%) pts, and avascular necrosis in 6 (8%) pts. Hepatic toxicity has resolved completely within two weeks in almost all pts as has the CNS toxicity. Grade III-IV hepatic toxicity have been transient. For pts 25 years of age and younger (n=25), the overall survival (OS) and disease free survival (DFS) at 2 years are 91% and 85% respectively. For pts > 25 years of age (n=15), the OS and DFS at 2 years are 55% and 61% respectively. This difference is statistically significant for the two groups; p=0.04 for DFS and p=0.004 for OS. Continued enrollment is anticipated to further evaluate the survival differences between these two patient groups.