The ex vivo production of ammonia predicts l-asparaginase biological activity in children with acute lymphoblastic leukemia

Shizuka Watanabe, Kumiko Miyake, Chitose Ogawa, Haruna Matsumoto, Kenichi Yoshida, Shinsuke Hirabayashi, Daisuke Hasegawa, Tadao Inoue, Junko Kizu, Reiko MacHida, Akira Ohara, Ryota Hosoya, Atsushi Manabe

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6 Citations (Scopus)

Abstract

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 μg/dL (170-345 μg/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.

Original languageEnglish
Pages (from-to)347-352
Number of pages6
JournalInternational journal of hematology
Volume90
Issue number3
DOIs
Publication statusPublished - 2009 Oct 1

Keywords

  • Acute lymphoblastic leukemia
  • Ammonia
  • Asparaginase
  • Children
  • Silent inactivation

ASJC Scopus subject areas

  • Hematology

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    Watanabe, S., Miyake, K., Ogawa, C., Matsumoto, H., Yoshida, K., Hirabayashi, S., Hasegawa, D., Inoue, T., Kizu, J., MacHida, R., Ohara, A., Hosoya, R., & Manabe, A. (2009). The ex vivo production of ammonia predicts l-asparaginase biological activity in children with acute lymphoblastic leukemia. International journal of hematology, 90(3), 347-352. https://doi.org/10.1007/s12185-009-0419-x