Monitoring of Erwinia asparaginase therapy in childhood ALL in the Nordic countries

Aims Evaluation of L-asparaginase therapy in the NOPHO-92 ALL-protocol (tre atment protocol of acute lymphoblastic leukaemia of the Nordic Society of P aediatric Haematology and Oncology, initiated in 1992) after intravenous an d intramuscular administration of Erwinia asparaginase during induction and re-induction therapy. Methods Forty children with newly diagnosed acute lymphoblastic leukaemia r eceived Erwinia asparaginase (30 000 IU/m(2) i.v. or i.m.) during induction therapy (every day for 10 days), and 19 children received Erwinia asparagi nase (30 000 IU/m(2) i.v. or i.m.) during re-induction therapy (twice a wee k for 2 weeks). Within the treatment periods asparaginase trough activity ( using a spectrophotometric assay) was determined on specific days. The goal of therapy is complete L-asparagine depletion, which asparaginase activiti es above 100 IU l(-1) have been shown to ensure. Therefore determination of L-asparagine (using a h.p.l.c. method) was performed only in plasma sample s with asparaginase activities below 100 IU l(-1). Results During induction therapy 92.2% of the trough enzyme activities were above 500 IU l(-1) for the i.v.-treated patients, and 92.4% of the trough enzyme activities were above 500 IU l(-1) for the i.m.-treated patients. Du ring re-induction therapy 64.7% of the trough enzyme activities were below 100 IU l(-1) in the i.v.-treated group, and 73.3% of the trough enzyme acti vities were below 100 IU l(-1) in the i.m.-treated group. For trough enzyme activities below 100 IU l(-1) L-asparagine depletion was complete in two t hirds of the samples. Conclusions In the NOPHO-92 ALL-protocol L-asparaginase treatment during in duction therapy was unnecessarily intense, but during the re-induction phas e it appeared inadequate.