Hashii Yoshiko, Yoshida Makoto, Hara Junichi, Nishimura Shinichiro, Yumura-Yagi Keiko, Horibe Keizo, Nakahata Tatsutoshi
Department of Pediatrics, Osaka University Graduate School of Medicine.
Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya.
J Pediatr Hematol Oncol. 2018 Jul;40(5):374-378. doi: 10.1097/MPH.0000000000001193.
L-Asparaginase has significantly improved outcome for children with acute lymphoblastic leukemia and has become an essential component of multiagent chemotherapy. However, there are many adverse events due to L-asparaginase, including acute pancreatitis. The pathology of L-asparaginase-associated pancreatitis (AAP) remains unclear. We compared patients who developed AAP (n=29) and random matched controls (n=36) who had been enrolled in the Japan Association of Childhood Leukemia Study of the ALL-02 protocol. AAP and control patients were matched for age, sex, treatment, and protocol risk. We examined correlations between AAP development and clinical symptoms, laboratory data, and concomitant medication. Abdominal pain and nausea were common presenting symptoms for AAP. There was an increased risk of AAP in patients using gastric acid-suppressing agents and antithrombin (AT) supplementation. Mean fibrinogen and AT levels before the onset of AAP were lower in AAP patients than in controls. Decreased AT and fibrinogen levels resulting from the strong suppression of protein synthesis by L-asparaginase were predictive signs for AAP. Our epidemiological approach should prove clinically useful for the diagnosis the AAP as early as possible.
左旋门冬酰胺酶显著改善了急性淋巴细胞白血病患儿的预后，已成为多药化疗的重要组成部分。然而，左旋门冬酰胺酶会引发许多不良事件，包括急性胰腺炎。左旋门冬酰胺酶相关性胰腺炎（AAP）的病理机制仍不清楚。我们比较了发生AAP的患者（n = 29）和参与日本儿童白血病协会ALL-02方案研究的随机匹配对照组（n = 36）。AAP患者和对照组在年龄、性别、治疗及方案风险方面进行了匹配。我们研究了AAP发生与临床症状、实验室数据及合并用药之间的相关性。腹痛和恶心是AAP常见的首发症状。使用胃酸抑制剂和补充抗凝血酶（AT）的患者发生AAP的风险增加。AAP患者在AAP发作前的平均纤维蛋白原和AT水平低于对照组。左旋门冬酰胺酶对蛋白质合成的强烈抑制导致AT和纤维蛋白原水平降低，是AAP的预测指标。我们的流行病学方法应证明对尽早诊断AAP具有临床实用性。
