The ex vivo production of ammonia predicts L-asparaginase biological activity in children with acute lymphoblastic leukemia.
Patients with acute lymphoblastic leukemia (ALL), who develop antiasparaginase antibodies without clinical allergic reactions ("silent inactivation") during L: -asparaginase (L: -Asp) treatment, have poor outcomes. Ammonia is produced by hydrolysis of asparagine by L: -Asp. We postulated that plasma ammonia level might reflect the biological activity of L: -Asp. Five children with ALL treated according to the Tokyo Children's Cancer Study Group (TCCSG) protocol were enrolled. Plasma ammonia levels were analyzed immediately and 1 h after incubation at room temperature and "ex vivo ammonia production" was defined as increase in ammonia concentration. Ex vivo ammonia production well correlated with L: -Asp activity (r = 0.882, P < 0.01, n = 23). It always exceeded 170 microg/dL (170-345 microg/dL) in induction therapy. We found 3 patients whose ammonia production was negligible during later phases of therapy. Antiasparaginase antibody was detected and L: -Asp activity decreased in these patients. Ex vivo ammonia production is a surrogate marker of L: -Asp biological activity.
Watanabe
Shizuka
S
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.|Department of Pharmacy, St. Luke's International Hospital, Tokyo, Japan.|Department of Practical Pharmacy, Keio University, Tokyo, Japan.
Miyake
Kumiko
K
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.|Department of Practical Pharmacy, Keio University, Tokyo, Japan.
Ogawa
Chitose
C
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Matsumoto
Haruna
H
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.|Department of Practical Pharmacy, Keio University, Tokyo, Japan.
Yoshida
Kenichi
K
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Hirabayashi
Shinsuke
S
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Hasegawa
Daisuke
D
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Inoue
Tadao
T
Department of Pharmacy, International University of Health and Welfare, Tokyo, Japan.
Kizu
Junko
J
Department of Practical Pharmacy, Keio University, Tokyo, Japan.
Machida
Reiko
R
First Department of Pediatrics, Toho University, Tokyo, Japan.
Ohara
Akira
A
First Department of Pediatrics, Toho University, Tokyo, Japan.
Hosoya
Ryota
R
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.
Manabe
Atsushi
A
Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan. manabe-luke@umin.ac.jp.
D000641:Ammonia / Q000097:blood*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D001215:Asparaginase / Q000276:immunology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D011446:Prospective Studies
D000970:Antineoplastic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D000641:Ammonia; D001215:Asparaginase