地西他滨治疗难治性贫血伴有原始细胞过多的疗效和不良反应与治疗疗程数的关系  

Analysis of the impact of decitabine treatment cycles on efficacy and safety in patients of myelodysplastic syndrome-refractory anemia with excess blasts

作　　者：雒雪萍 徐泽锋[1] 秦铁军 张悦 张宏丽 方力维 潘丽娟 胡耐博 曲士强 李冰 肖志坚 

机构地区：[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院,实验血液学国家重点实验室,天津300020

出　　处：《中华血液学杂志》2016年第10期870-875,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81270585、81370611、81470297、81530008）;协和学者与创新团队发展计划

摘　　要：目的评估地西他滨治疗骨髓增生异常综合征（MDS）难治性贫血伴有原始细胞过多（RAEB）患者的疗效和不良反应与治疗疗程数的关系。方法2008年12月至2016年3月中国医学科学院血液病医院MDS诊疗中心共有56例RAEB患者接受了地西他滨20 mg·m^-2·d^-1×5 d方案治疗，回顾性分析其临床特征、疗效、疗效影响因素及不良反应。结果RAEB-1 25例，RAEB-2 31例。中位治疗3（1-15）个疗程。总有效[完全缓解（CR）＋骨髓完全缓解（mCR）＋血液学改善（HI）]率为67.9%（38/56），其中10例（17.8%）CR, 8例（14.3%）mCR但无HI，17例（30.4%）mCR同时有HI, 3例（5.4%）单纯HI。中位随访7.9（1.0- 56.3）个月，中位生存期为21.1（95%CI 16.0- 26.1）个月。RAEB-1患者的疗效（总有效率为88.0%）显著优于RAEB-2患者（总有效率为51.6%）（P=0.004），多因素分析证实其为影响疗效的独立预后因素（OR=6.03，95%CI 1.39-26.09，P=0.016）。地西他滨治疗有效的38例患者中，37例（97.4%）在1-2个疗程起效，25例（65.8%）在2个疗程内达到最佳疗效，37例（97.4%）在4个疗程内达最佳疗效。主要不良反应为3级以上血细胞减少及感染，在治疗早期（第1-2疗程）中较常见，治疗有效后随疗程增加，发生率逐渐下降，其他非血液学不良反应发生率低。结论地西他滨标准剂量5天方案治疗RAEB疗效肯定。治疗有效患者常在第1-2个疗程起效，4个疗程内达最佳疗效。主要不良反应为血细胞减少及感染，常见于前2个疗程，起效后后续疗程不良反应发生率显著降低。ObjectiveTo explore the impact of decitabine treatment cycles on efficacy and adverse events（AEs）in patients of myelodysplastic syndrome-refractory anemia with excess blasts（MDSRAEB）.MethodsA total of fifty-six patients with MDS-RAEB who received decitabine 20 mg·m^-2·d^-1by IV infusion daily for 5 consecutive days every 4 weeks at a single institute in China were enrolled from December 2008 to March 2016. Their clinical features, efficacy, predictors of efficacy and AEs were analyzed retrospectively.ResultsOf the 56 patients enrolled, 25 cases were MDS-RAEB1, another 31 were MDS-RAEB2. A median of 3 cycles（range, 1-15 cycles）were delivered. The overall response rate was 67.9%（10 complete responses, 8 marrow complete responses without hematologic improvement, 17 marrow complete responses with hematologic improvements, and 3 hematologic improvements）. With a median follow-up duration of 7.9（1.0-56.3）months, the median overall survival was 21.1（95% CI 16.0-26.1）months. Compared with RAEB-2, RAEB-1 predicted higher overall response rates in a multivariate analysis. Of the 38 patients who experienced clinical responses, initial responses were detected by the end of two cycles in 37 patients. Twenty-five of the 38 patients who experienced clinical responses had their best response within the first two cycles, and 37 cases of the patients achieved best response by the end of fourth cycles. Grade 3 or 4 cytopenia and infection were the most prevalent AEs, which occurred frequently in the early courses and decreased later, and other non-hematologic AEs were rare.ConclusionDecitabine treatment was favorable in patients with MDS-RAEB. In most of the cases, initial responses were observed within 2 cycles, and best response was achieved by the end of 4 th cycles. The most common AEs were grade 3 or 4 cytopenia and infection, which were observed frequently in first 2 cycles and decreased later as objective response were achieved.

关 键 词：骨髓增生异常综合征 地西他滨 治疗结果 药物毒性 

分 类 号：R551.3[医药卫生—血液循环系统疾病] R556[医药卫生—内科学]