Yoshida Hideki, Imamura Toshihiko, Saito Akiko M, Takahashi Yoshihiro, Suenobu So-ichi, Hasegawa Daiichiro, Deguchi Takao, Hashii Yoshiko, Kawasaki Hirohide, Endo Mikiya, Hori Hiroki, Suzuki Nobuhiro, Kosaka Yoshiyuki, Kato Koji, Yumura-Yagi Keiko, Hara Junichi, Oda Megumi, Sato Atsushi, Horibe Keizo
Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
PLoS One. 2015 Aug 28;10(8):e0136428. doi: 10.1371/journal.pone.0136428. eCollection 2015.
Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10-15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥ 10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (P<0.01), especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients.
虽然L-天冬酰胺酶相关的高血糖是一种众所周知的不良事件，但尚未研究这种不良事件的特征是否会受到L-天冬酰胺酶给药强化的影响。在此，我们分析了1176例根据日本儿童白血病研究协会ALL-02方案治疗的小儿急性淋巴细胞白血病患者中L-天冬酰胺酶相关高血糖的特征，这些患者在维持期使用了延长的L-天冬酰胺酶给药。我们确定共有69例患者发生了75次L-天冬酰胺酶相关高血糖事件。虽然诱导期发生了17次事件（17/1176，1.4%），这一发生率低于先前报告中的发生率（10 - 15%），但在维持期延长L-天冬酰胺酶给药期间发生了45次事件。多因素分析表明，发病时年龄较大（≥10岁）是L-天冬酰胺酶相关高血糖的唯一独立危险因素（P<0.01），尤其是在维持期。与先前的报告相反，肥胖与L-天冬酰胺酶相关高血糖无关。这些发现表明，在治疗青少年和年轻成人急性淋巴细胞白血病患者时，延长L-天冬酰胺酶给药是高血糖的危险因素。
