超小剂量地西他滨治疗骨髓增生异常综合征37例疗效及安全性评价

Efficacy and safety of an ultra low dose of decitabine in the treatment of patients with myelodysplastic syndromes in 37 cases

目的探讨超小剂量地西他滨方案治疗骨髓增生异常综合征(MDS)的临床疗效及安全性。方法收集2014年1月至2015年10月江苏省人民医院血液科收治接受地西他滨治疗可评价的MDS患者37例。皮下注射地西他滨(每日5~7 mg/m2,治疗第1~3天,第8、15、22天),每4周为1个疗程,连续4~6个疗程。比较不同预后分组间疗效差异,评价可能与疗效相关的参数。结果 20例(54%)获得了临床反应,其中2例(5.4%)完全缓解,骨髓完全缓解无血液学改善1例(2.7%),骨髓完全缓解伴血液学改善1例(2.7%),血液学改善14例(37.8%),脱离输血2例(5.4%);疾病稳定14例(37.8%),疾病进展3例(8.1%)。按WPSS预后分层分组,较低危组与较高危组之间总反应率差异有统计学意义(70.0%对35.3%,χ~2=4.457,P=0.035);按IPSS-R细胞遗传学分层,预后良好组与中危组、高危组之间总反应率差异有统计学意义(60%对25%,χ~2=6.036,P=0.014);根据查尔森合并症指数(CCI)分组,各组间疗效差异无统计学意义。Ⅲ~Ⅳ度骨髓抑制13例(35.1%);在粒细胞缺乏期9例(24.3%)(Ⅱ~Ⅳ度)发生感染性发热;没有因血液学毒性而死亡;未观察到Ⅲ~Ⅳ级胃肠道及心、肝、肾等毒副反应。骨髓抑制、发热等不良反应根据CCI危险分层比较,低危、中危及高危之间不良反应发生率差异无统计学意义(P>0.05)。结论超小剂量地西他滨方案治疗MDS疗效佳,且耐受性良好,低、中危组MDS疗效好于高危组。有合并症不影响疗效。

Objective To evaluate the clinical efficacy and safety of an ultra low dose of decitabine in the treatment of patients with myelodysplastic syndromes. Methods Totally 37 patients received the treatment of ultra low dose of decitabine, （5-7 mg/m^2/d） on d1-3, d8, d15 and d22, each cycle lasting for 4 weeks, in our hospital from January 2014 and October 2015. The treatment lasted continuously for 4-6 cycles. The clinical effects and adverse reactions of the regimen were evaluated. Results Twenty patients （54%） were responsive to decitabine after a median of 4 courses （range 1-6） of treatment. There were 2 cases （5.4%） with complete remission （CR）, marrow CR （mCR） without hematological improvement （HI） in 1 case（2.7%）, mCR with HI in 1 case（2.7%）, and HI alone in 14 cases（37.8%）; 2 cases（5.4%） achieved transfusion independence, and 14 cases（37.8%） with stable disease （SD） and 3 cases（8.1%） with progressive disease. Among the 14 patients with abnormal chromosome, 3 patients （21.4%） achieved cytogenetic response （CR）, 1 patients （7.1%） achieved a cytogenetic partial response （cPR） after one course of decitabine. ORR difference （Х^2=4.457, P=0.03S） was significant between lower-risk and higher-risk group by WPSS prognostic stratification. Thses was statistical difference between the good and intermediate, poor prognosis groups （Х^2=6.036, P=0.014） according IPSS-R cytogenetic stratification. Ⅲ-Ⅳ grade of myelosuppression developed in 13 cases（35.1%） according to WHO side-effects criteria. No Ⅲ -Ⅳgrade of heart and gastrointestinal tract, liver, kidney or other side effects were observed. No statistical difference was observed on the efficiency and adverse reaction among groups classified by Charlson comorbidity index （CCI）.. Conclusion Ultra low dose of decitabine is efficient, responsive and safe for MDS patients, especially for those with severe comorbidity.