Asparaginase is a cornerstone in the treatment of ALL. In most contemporary protocols like in NOPHO ALL2008 prolonged asparaginase treatment has been implemented.

Publish data from NOPHO ALL2008 show sufficient treatment of the majority of patients (analysing trough levels of asparaginase after 2 weeks) but 13% of the patients experience an allergic reaction to this foreign protein (85% of them after the 2nd or 3rd dose) and they have no enzyme activity even before the reaction, meaning that they don't benefit from the treatment at all. In addition 4-5% of the patients have no enzyme activity through the whole treatment without hypersensitivity symptoms. So in reality approximately 20% of the patients don't receive any asparaginase treatment. Therapeutic Drug Monitoring (TDM) of asparaginase has been established in Aarhus, Denmark, under the leadership of Birgitte Klug Albertsen (BKA). From February 2017 the centers have been invited to send samples (extended sampling) in order to gain more knowledge about the pharmacokinetics, to identify patients without activity and to establish the logistics for TDM of asparaginase, which will be mandatory in the next protocol ALLTogether, presumably opening in 2018.

From February 2016 an extended sampling for enzyme activity measurements was started and will continue until NOPHO ALL2008 closes. These samples will make it possible to do more in depth pharmacokinetic studies as well as identify the optimal sampling time points for identifying no-activity patients in the future.

A database is being developed for TDM in ALLTogether, but it will also include all the asparaginase measurements in ALL2008.

Inclusion Criteria:

• ALL treated on the NOPHO ALL2008 protocol, age 1-45 years.

Exclusion Criteria:

• No samples sent

Alle patients in the NOPHO countries aged 1-45 years treated for ALL on the NOPHO ALL2008 protocol and have asparaginase-activity-samples sent to Aarhus.