Peg-Asparaginase In Adult Acute Lymphoblastic Leukemia (All): Efficacy And Feasibility Analysis With Increasing Dose Levels

Asparaginase (ASP) has a unique role in the treatment of ALL, and several pediatric studies have demonstrated that modifications of schedule, preparation and dose of ASP may have an impact on overall outcome. The optimisation of ASP treatment is therefore an important aim of the German Multicenter Study Group for Adult ALL (GMALL). In 1999 a pilot trial for adult ALL was started (GMALL 06/99), followed by the ongoing main trial 07/2003. Induction comprised dexamethasone, vincristine, daunorubicine and i.th. methotrexate. One dose of pegylated ASP (PEG-ASP) 1000 U/m2 (500 U/m² if > 55yrs) was given instead of 7 doses of 5000 U/m2 native E.coli asparaginase (ASP) given over 14 days in previous GMALL studies. In consolidation one dose PEG-ASP (500 U/m2) replaced one dose of E.coli ASP (10000 U/m2) in combination with high-dose methotrexate (1500 U/m²) and mercaptopurine. ASP activity was above 100 U/l at day 10 in 80% of the pts after 1000U/m2 and in only 42% after 500 U/m2. Based on this correlation between dose and duration of activity in study 07/2003 (amendment II in 12/2006) the dose for PEG-ASP was increased to 2000 U/m2 in induction and consolidation for pts < 55 yrs and to 1000 U/m2 for pts > 55 yrs in order to improve treatment efficacy. Details of the protocol have been reported (Brüggemann, Blood 2006: 107;1116).