Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia (ALL) Treated with Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy
Authors: Rytting Michael E. , Thomas Deborah A. , Jabbour Elias , Franklin Anna R.K. , Borthakur Gautam , Faderl Stefan , Schroeder Kurt , Ravandi Farhad , Garris Rebecca , o'Brien Susan , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 1527
Several pediatric-based protocols for treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults have been completed or are ongoing. Some studies have enrolled patients (pts) up to age 55 years, and, so far, results have been satisfactory. Augmented Berlin-Frankfurt-Muenster (ABFM) has been shown to be an effective and tolerable treatment for ALL in adolescents. To evaluate the efficacy and toxicity of this therapy in young adults, we designed a protocol of modified ABFM therapy for pts with ALL from age 12 to 40 years old. 83 pts have been enrolled on protocol and are evaluable for toxicity. 68 pts with de novo Philadelphia chromosome negative ALL have completed at least 29 days of therapy (induction) on protocol. They have the following characteristics: 56 (82%) pts have pre-B ALL and 12 (18%) have T-ALL. The median age is 21 (mean=23; range=13–39). The median presenting WBC=5.3 (mean=32; range= 0.4–494). 65/68 (96%) pts have achieved a remission. One patient died during induction. 50 (74%) pts have attained remission by 15 days of induction, while 15 (22%) have been slow responders. 5/68 (7%) pts have required an extension of induction by 2 weeks. At day 29 of therapy, 38 (56%) pts had negative minimal residual disease (MRD) by flow cytometry, 20 (29%) patients were positive for MRD, 10 were suspicious or not available. By day 84 of therapy, 49 (72%) pts were negative for MRD and 9 (13%) were positive. Currently, there have been 17 relapses and 10 deaths. Toxicities in the entire group include severe asparaginase allergy in 15 (18%) pts, thrombus formation in 16 (19%) pts, hyperbilirubinemia grade III-IV in 19 (23%) pts, ALT/AST grade III-IV in 23 (28%) pts, CNS stroke-like symptoms in 6 (7%) pts, hypofibrinogen grade III-IV in 26 (31%), pancreatitis in 6 (7%), and avascular necrosis in 6 (7%) pts. Hepatic toxicity has resolved completely within two weeks in almost all pts as has the CNS toxicity. In summary, induction success, by morphology and flow cytometry, has been satisfactory with this regimen. CRD and OS have not been significantly better than with HyperCVAD therapy for this age group. Expected toxicities have been prominent, but mostly transient. Hypofibrinogenemia is frequent, but bleeding is rare. Thrombosis and severe allergic reactions are more frequent than in pediatric trials. For pts 25 years of age and younger, the overall survival (OS) and disease free survival (DFS) at 2 years are 88% and 84% respectively. For pts > 25 years of age, the OS and DFS at two years are 65% and 50% respectively. This difference in OS between the groups is statistically significant. Continued enrollment is anticipated to further evaluate the survival differences between these two patient groups.

Disclosures:
No relevant conflicts of interest to declare.