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

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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.

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Authors and Affiliations

  1. Department of Pediatrics, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan

    Shizuka Watanabe, Kumiko Miyake, Chitose Ogawa, Haruna Matsumoto, Kenichi Yoshida, Shinsuke Hirabayashi, Daisuke Hasegawa, Ryota Hosoya & Atsushi Manabe

  2. Department of Pharmacy, St. Luke’s International Hospital, Tokyo, Japan

    Shizuka Watanabe

  3. Department of Practical Pharmacy, Keio University, Tokyo, Japan

    Shizuka Watanabe, Kumiko Miyake, Haruna Matsumoto & Junko Kizu

  4. Department of Pharmacy, International University of Health and Welfare, Tokyo, Japan

    Tadao Inoue

  5. First Department of Pediatrics, Toho University, Tokyo, Japan

    Reiko Machida & Akira Ohara

Authors
  1. Shizuka Watanabe
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  2. Kumiko Miyake
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  3. Chitose Ogawa
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  4. Haruna Matsumoto
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  5. Kenichi Yoshida
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  6. Shinsuke Hirabayashi
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  7. Daisuke Hasegawa
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  8. Tadao Inoue
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  9. Junko Kizu
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  10. Reiko Machida
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  11. Akira Ohara
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  12. Ryota Hosoya
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  13. Atsushi Manabe
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Corresponding author

Correspondence to Atsushi Manabe.

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Watanabe, S., Miyake, K., Ogawa, C. et al. The ex vivo production of ammonia predicts l-asparaginase biological activity in children with acute lymphoblastic leukemia. Int J Hematol 90, 347–352 (2009). https://doi.org/10.1007/s12185-009-0419-x

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  • DOI: https://doi.org/10.1007/s12185-009-0419-x

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