阿扎胞苷不同诱导方案治疗老年急性髓系白血病多中心前瞻性研究

Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia

目的:探讨相同总剂量下阿扎胞苷(Aza)标准用药(标准剂量组)与低剂量长疗程(调整剂量组)不同诱导方案治疗老年急性髓系白血病的有效性及安全性。方法:选取2020年1月至2021年6月收治的103例采用Aza治疗的老年急性髓系白血病(非急性早幼粒细胞白血病)患者为研究对象。标准剂量组50例患者,Aza按标准用药剂量75 mg/(m^(2)·d)给药7 d,调整剂量组53例患者,按100 mg/d给药7-12 d(按患者单疗程标准用药总量计算用药天数),两组患者均可Aza单药或联合用药,分析Aza不同诱导方案对患者的有效性及安全性影响。在两组内分别进行单药、联合BCL-2抑制剂和联合低剂量化疗亚组分析,进一步探讨Aza单药与Aza联合不同药物间的有效性和安全性差异。结果:标准剂量组与调整剂量组间的有效率、不良反应发生率及1年总体生存率比较无显著差异(P>0.05);联合用药有效率较Aza单药更高(P<0.05),但联合BCL-2抑制剂与联合低剂量化疗间的有效率比较无显著差异(P>0.05)。联合BCL-2抑制剂较Aza单药并不会增加不良反应的发生率。联合低剂量化疗较联合BCL-2抑制剂和Aza单药存在更高的骨髓抑制及肺部感染的风险(P<0.05)。Aza单药、联合BCL-2抑制剂和联合低剂量化疗间的1年总体生存率未见显著差异(P>0.05)。结论:两种用药方案均可用于不能耐受强化疗的老年急性髓系白血病患者,且总有效性及安全性相近。Aza联合低剂量化疗可使患者有效率提高,但也会增加严重不良反应发生率,且与单药相比可能并不会使患者获得更长的生存期。Aza联合BCL-2抑制剂较联合低剂量化疗在完全缓解、总体客观缓解率及总体生存方面相似,但安全性更高。

Objective:To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine(Aza),including standard dose(standard dose group)and low-dose long-term(adjusted dose group),in the treatment of elderly acute myeloid leukemia(AML).Methods:A total of 103 elderly patients with AML(non-acute promyelocytic leukemia)from January 2020 to June 2021 were enrolled.Aza was administered at the standard dose of 75 mg/(m2·d)for 7 days in the standard dose group(50 cases),while at 100 mg/d for 7-12 days in the adjusted dose group(53 cases).The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment.The efficacy and safety between standard dose group and adjusted dose group were compared.Subgroup analysis were performed in the two groups for Aza alone,Aza combined with BCL-2 inhibitor,and Aza combined with low-dose chemotherapy for efficacy and safety.Results:There were no significant differences in overall response rate(ORR),incidence of adverse reaction,and 1-year overall survival(OS)rate between standard dose group and adjusted dose group(P>0.05).The ORR of combination was higher than that of Aza alone(P<0.05),while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy(P>0.05).The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone.There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone(P<0.05).No significant difference was observed in 1-year OS between Aza alone,Aza combined with BCL-2 inhibitor,and Aza combined with low-dose chemotherapy(P>0.05).Conclusions:Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety.Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions,and may not result in longer survival compared with Aza alone.Aza combined with BCL-2 inhibitor not only has similar effect in complete remission,objective response rate,and OS compared with Aza combined with low-dose chemotherapy,but also has higher safety.