高剂量阿糖胞苷与胃肠道和小脑毒性有关，妨碍其在老年或身体不适的急性髓系白血病 (AML) 患者中使用。 Aspacytarabine 是阿糖胞苷的一种无活性前药，在一项 2b 期研究中，对不适合强化化疗的 AML 患者作为单一疗法进行了评估 (NCT03435848)。 65 名 AML 患者接受天冬氨酸阿糖胞苷 4.5 g/m2/d（相当于 3 g/m2/d 阿糖胞苷）治疗，每个疗程 6 剂。中位年龄为 75 岁； 60.6% 患有新发 AML，28.8% 患有继发于骨髓增生异常综合征的 AML，10.6% 患有治疗相关 AML。总体而言，36.9% 的患者实现了完全缓解 (CR)，计数完全恢复。继发性 AML 患者、既往接受过低甲基化药物治疗的患者以及 TP53 突变患者的 CR 率分别为 26.7%、25% 和 36%。中位总生存期为 9 个月（范围 6 至 15.9），但应答者尚未达到这一目标。到第 26 天，所有有反应的患者均观察到血液学恢复，没有出现长期血细胞减少。没有观察到通常妨碍老年或身体不适患者使用大剂量阿糖胞苷的不良事件。 Aspacytarabine 似乎是一种有效的治疗方案，可减少与高剂量阿糖胞苷相关的伴随毒性，这是治疗使用高剂量阿糖胞苷的 AML 和其他血液疾病时的一个重要考虑因素。版权所有 © 2023 美国血液学会。

High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity precluding its use in older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study, in patients with AML unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2/d (equimolar to 3 g/m2/d cytarabine) for 6 doses per treatment courses. The median age was 75 years; 60.6% had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome and 10.6% therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents and patients with TP53-mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range 6 to 15.9) and not reached among responders. Hematologic recovery was observed in all responding patients by day 26 with no prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. Aspacytarabine appears to be an effective regimen, with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine.Copyright © 2023 American Society of Hematology.