TY - JOUR
T1 - How much asparaginase is needed for optimal outcome in childhood acute lymphoblastic leukaemia? A systematic review
AU - Brigitha, Leiah J.
AU - Pieters, Rob
AU - van der Sluis, Inge M.
N1 - Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - This review focuses on asparaginase, a key component of childhood acute lymphoblastic leukaemia (ALL) treatment since the 1970s. This review evaluates how much asparaginase is needed for optimal outcome in childhood ALL. We provide an overview of asparaginase dose intensity, i.e. duration of total cumulative exposure in weeks and level of exposure reflected by dose and/or asparaginase activity level, and the corresponding outcome. We systematically searched papers published between January 1990 and March 2021 in the PubMed and MEDLINE databases and included 20 papers. The level and duration of exposure were based on the pharmacokinetic profile of the drug and the assumption that trough asparaginase activity levels of ≥100 IU/L should be achieved for complete L-asparagine depletion. The statistical meta-analysis of outcomes was not performed because different outcome measures were used. The level of exposure was not associated with the outcome as long as therapeutic asparaginase activity levels of ≥100 IU/L were reached. Conflicting results were found in the randomised controlled trials, but all truncation studies showed that the duration of exposure (expressed as weeks of L-asparagine depletion) does affect the outcome; however, no clear cutoff for optimal exposure duration was determined. Optimal exposure duration will also depend on immunophenotype, (cyto)genetic subgroups, risk group stratification and backbone therapy.
AB - This review focuses on asparaginase, a key component of childhood acute lymphoblastic leukaemia (ALL) treatment since the 1970s. This review evaluates how much asparaginase is needed for optimal outcome in childhood ALL. We provide an overview of asparaginase dose intensity, i.e. duration of total cumulative exposure in weeks and level of exposure reflected by dose and/or asparaginase activity level, and the corresponding outcome. We systematically searched papers published between January 1990 and March 2021 in the PubMed and MEDLINE databases and included 20 papers. The level and duration of exposure were based on the pharmacokinetic profile of the drug and the assumption that trough asparaginase activity levels of ≥100 IU/L should be achieved for complete L-asparagine depletion. The statistical meta-analysis of outcomes was not performed because different outcome measures were used. The level of exposure was not associated with the outcome as long as therapeutic asparaginase activity levels of ≥100 IU/L were reached. Conflicting results were found in the randomised controlled trials, but all truncation studies showed that the duration of exposure (expressed as weeks of L-asparagine depletion) does affect the outcome; however, no clear cutoff for optimal exposure duration was determined. Optimal exposure duration will also depend on immunophenotype, (cyto)genetic subgroups, risk group stratification and backbone therapy.
KW - Acute lymphoblastic leukaemia
KW - Asparaginase
KW - Dose intensity
KW - Outcome
KW - Pediatric ALL
UR - http://www.scopus.com/inward/record.url?scp=85114912417&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.08.025
DO - 10.1016/j.ejca.2021.08.025
M3 - Review article
C2 - 34536947
AN - SCOPUS:85114912417
SN - 0959-8049
VL - 157
SP - 238
EP - 249
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -