Kenichi Sakamoto and Toshihiko Imamura, Kyoto Prefectural University of Medicine; Hidefumi Hiramatsu, Kyoto University, Kyoto; Kenichi Sakamoto, Toshihiko Imamura, Akiko Moriya-Saito, and Keizo Horibe, National Hospital Organization Nagoya Medical Center; Koji Kato, Japanese Red Cross Nagoya First Hospital, Nagoya; Kentaro Kihira and Hiroki Hori, Mie University, Mie; Koji Suzuki, University of Fukui Faculty of Medical Sciences, Fukui; Hisashi Ishida, Okayama University, Okayama; Hiromi Morita, University of Occupational and Environmental Health, Iseigaoka; Miyako Kanno, Yamagata University, Yamagata; Takeshi Mori, Kobe University; Kousaku Matsubara, Kobe City Nishi-Kobe Medical Center; Daiichiro Hasegawa and Yoshiyuki Kosaka, Hyogo Prefectural Children's Hospital, Kobe; Kiminori Terui, Hirosaki University, Hirosaki; Yoshihiro Takahashi, Aomori Prefectural Central Hospital, Aomori; So-ichi Suenobu, Oita University, Oita; Atsushi Sato, Miyagi Children's Hospital, Sendai; Hirohide Kawasaki, Kansai Medical University; Keiko Yumura-Yagi, Yumura Clinic; and Junichi Hara, Osaka City General Hospital, Osaka, Japan.
J Clin Oncol. 2018 Mar 20;36(9):900-907. doi: 10.1200/JCO.2017.75.5066. Epub 2018 Jan 23.
Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age (≥ 10 years) was the sole significant risk factor for ON ( P < .001). Separate evaluation of patients ≥ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and 5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and l-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age (≥ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and l-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.
目的 骨坏死（ON）是儿童急性淋巴细胞白血病（ALL）治疗的严重并发症；然而，亚洲儿科 ALL 患者的 ON 数据很少。因此，我们对日本 ALL 患者的两个队列进行了回顾性分析，以阐明 ON 的发生率、临床特征和危险因素。
患者和方法 在日本儿童白血病研究协会（JACLS）组的两项研究中（分别接受 ALL-97 和 ALL-02 方案治疗的 635 例和 1027 例患者），确定了 ALL（n=1662）患者中 ON 的发生率和特征。
结果 1662 例患者中共有 24 例发生 ON，其中 ALL-97 方案治疗的 635 例患者中有 12 例，ALL-02 方案治疗的 1027 例患者中有 12 例。24 例患者中，23 例年龄大于 10 岁。多因素分析显示，年龄（≥10 岁）是 ON 的唯一显著危险因素（P<0.001）。≥10 岁患者的单独评估表明，ON 的 5 年累积发生率分别为 ALL-97 方案的 7.2%（95%CI，4.0%至 12.6%）和 ALL-02 方案的 5.9%（95%CI，3.3%至 10.4%），尽管接受了与可比研究相似的地塞米松（DEX）治疗，但低于先前报告的发生率；然而，JACLS 方案中同时使用 DEX 和 L-门冬酰胺酶的情况减少了。
结论 我们在 JACLS ALL-97 和 ALL-02 研究中发现了 ON 的低发生率。尽管 ON 的唯一危险因素是年龄（≥10 岁），但即使在高危患者中，ON 的发生率也明显低于以往研究报告的发生率。这些结果表明，不仅 DEX 的总量，而且 DEX 和 L-门冬酰胺酶的给药方式（影响 DEX 的清除率），可能与 ALL 患者的 ON 发生率有关。
