Elimination of l-asparaginase in children treated for acute lymphoblastic leukemia.
The elimination of l-asparaginase (l-Asp) was studied in 8 children treated for acute lymphoblastic leukemia according to the CoALL 82 protocol. The patients received four doses of l-Asp as a single agent during induction chemotherapy. We studied the elimination of l-Asp during the first infusion in 1 child, during the second in 3, during the third in 2 and during the forth in 2 children. Using Western blot technique and an experimental rabbit antibody to l-Asp, we were able to detect a single band at 32 kilodaltons (KD) in the serum of all patients between 4 and 36 h after infusion. The molecular weight remained unchanged and no other bands occurred during the time of observation. The detection limit of this method was calculated to 5 micrograms/ml using radial immunodiffusion. Incubation of l-Asp with pooled normal human serum caused no degradation of the enzyme during 48 h at 37 degrees C. Neither the total enzyme nor fragments were detectable in the urine of the patients collected during 8 h after l-Asp infusion. From these results we conclude that l-Asp is not cleaved by proteases in humans. The enzyme is most probably eliminated by the reticuloendothelial system.
Brueck
M
M
Department of Neonatology and Gastroenterology, Children's Hospital, University of Düsseldorf, FRG.
Koerholz
D
D
Nuernberger
W
W
Juergens
H
H
Goebel
U
U
Wahn
V
V
D000293:Adolescent; D001215:Asparaginase / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D005779:Immunodiffusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*
D001215:Asparaginase