Department of Pediatrics, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.
Division of Pediatrics, Miyakonojo Medical Association Hospital, Miyakonojo, Japan.
Int J Hematol. 2024 Dec;120(6):725-734. doi: 10.1007/s12185-024-03856-3. Epub 2024 Sep 30.
Silent inactivation (SI) of L-asparaginase (ASP) is a phenomenon by which a neutralizing antibody for ASP (AAA) decreases ASP activity (ASA) in patients without a clinical allergy to ASP. Acute lymphoblastic leukemia (ALL) has a poor prognosis in patients with SI. Therefore, measurement of ASA levels, not AAA levels, is needed to identify patients with SI. We herein report the results of the prospective clinical trial ALL-ASP19, the first study in Japan to measure ASA and AAA to identify patients with SI. A total of 110 newly diagnosed ALL patients were enrolled, and ASA levels were measured three times during ALL treatment. Besides the 12 patients who discontinued the study, 32 were excluded due to inappropriate frequency and timing of ASA measurements and inappropriate ASP dosing. The remaining 66 patients were analyzed, and 3 patients with SI (4.5%) were identified. The incidence of SI is lower in Japan than in other countries. AAA was detected in all patients with SI, but four of the seven patients with AAA did not develop SI. Clinical characteristics did not significantly differ between patients with and without SI. Therefore, ASA levels must be measured to identify patients receiving insufficient ASP treatment.
L-天冬酰胺酶（ASP）的沉默失活（SI）是一种现象，即针对 ASP 的中和抗体（AAA）会降低无 ASP 临床过敏患者的 ASP 活性（ASA）。具有 SI 的急性淋巴细胞白血病（ALL）患者预后不良。因此，需要测量 ASA 水平，而不是 AAA 水平，以识别具有 SI 的患者。我们在此报告前瞻性临床试验 ALL-ASP19 的结果，这是日本首例测量 ASA 和 AAA 以识别 SI 患者的研究。共有 110 例新诊断的 ALL 患者入组，并在 ALL 治疗期间三次测量 ASA 水平。除了 12 名停止研究的患者外，由于 ASA 测量的频率和时间不合适以及 ASP 剂量不合适，还有 32 例被排除在外。对其余 66 例患者进行了分析，发现 3 例具有 SI（4.5%）。日本 SI 的发生率低于其他国家。在所有具有 SI 的患者中均检测到 AAA，但在具有 AAA 的七名患者中，有四名未发生 SI。具有和不具有 SI 的患者的临床特征无显著差异。因此，必须测量 ASA 水平以识别接受 ASP 治疗不足的患者。
