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

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• 作者：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)
  
• 关键词：Asparaginase ; Ammonia ; Acute lymphoblastic leukemia ; Children ; Silent inactivation
• 刊名：International Journal of Hematology
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：90
• 期：3
• 页码：347-352
• 全文大小：306KB
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• 作者单位：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)
  
  1. Department of Pediatrics, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan
  2. Department of Pharmacy, St. Luke’s International Hospital, Tokyo, Japan
  3. Department of Practical Pharmacy, Keio University, Tokyo, Japan
  4. Department of Pharmacy, International University of Health and Welfare, Tokyo, Japan
  5. First Department of Pediatrics, Toho University, Tokyo, Japan
  

文摘

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 (170-45?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.