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International Journal of Hematology

, Volume 90, Issue 3, pp 347–352 | Cite as

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 ManabeEmail author
Original Article

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.

Keywords

Asparaginase Ammonia Acute lymphoblastic leukemia Children Silent inactivation 

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Copyright information

© The Japanese Society of Hematology 2009

Authors and Affiliations

  • Shizuka Watanabe
    • 1
    • 2
    • 3
  • Kumiko Miyake
    • 1
    • 3
  • Chitose Ogawa
    • 1
  • Haruna Matsumoto
    • 1
    • 3
  • Kenichi Yoshida
    • 1
  • Shinsuke Hirabayashi
    • 1
  • Daisuke Hasegawa
    • 1
  • Tadao Inoue
    • 4
  • Junko Kizu
    • 3
  • Reiko Machida
    • 5
  • Akira Ohara
    • 5
  • Ryota Hosoya
    • 1
  • Atsushi Manabe
    • 1
    Email author
  1. 1.Department of PediatricsSt. Luke’s International HospitalTokyoJapan
  2. 2.Department of PharmacySt. Luke’s International HospitalTokyoJapan
  3. 3.Department of Practical PharmacyKeio UniversityTokyoJapan
  4. 4.Department of PharmacyInternational University of Health and WelfareTokyoJapan
  5. 5.First Department of PediatricsToho UniversityTokyoJapan

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