TY - JOUR
T1 - Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group
AU - van der Sluis, Inge M.
AU - de Groot-Kruseman, Hester
AU - te Loo, Maroeska
AU - Tissing, Wim J. E.
AU - van den Bos, Cor
AU - Kaspers, Gertjan J. L.
AU - Bierings, Marc
AU - Kollen, Wouter J. W.
AU - König, Thorsten
AU - Pichlmeier, Uwe
AU - Kühnel, Hans-J. rgen
AU - Pieters, Rob
PY - 2018
Y1 - 2018
N2 - Background: The efficacy and safety of recombinant Escherichia coli–asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). Methods: One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase). Results: Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti-asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5-year event-free survival, and 5-year cumulative incidence of relapse did not differ between both groups. Conclusion: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006-003180-31.
AB - Background: The efficacy and safety of recombinant Escherichia coli–asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). Methods: One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase). Results: Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti-asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5-year event-free survival, and 5-year cumulative incidence of relapse did not differ between both groups. Conclusion: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006-003180-31.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046358625&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29727043
U2 - https://doi.org/10.1002/pbc.27083
DO - https://doi.org/10.1002/pbc.27083
M3 - Article
C2 - 29727043
SN - 1545-5009
VL - 65
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 8
M1 - e27083
ER -