Outcome Following Truncation of Asparaginase

Overall survival for children with ALL is now above 90% in several protocols, but asparaginase associated toxicities still constitutes a significant problem as they, besides causing acute morbidity and mortality, can cause truncation of treatment with a subsequent increased risk of relapse. The most frequent toxicities causing asparaginase truncations are hypersensitivity, pancreatitis and thrombosis. Especially hypersensitivity constitutes a problem due to silencing antibodies, not only in patients with clinical hypersensitivity but also in patients without clinical symptoms (silent inactivation). In the NOPHO ALL2008 protocol asparaginase associated toxicities and truncation of asparaginase have been registered since the protocol opened in 2008. In addition asparaginase enzyme activity measurements have been done before every asparaginase administration and analyzed retrospectively. The primary aim of this study was to investigate if patients with truncation of asparaginase or lack of asparaginase enzyme activity had a different risk of relapse compared to patients who received full asparaginase treatment. Secondary we aimed to explore if patients who received less than 50% of their planned asparaginase dosages had a different risk of relapse compared to those who received 50% or more.