小剂量马法兰治疗中、高危骨髓增生异常综合征临床疗效观察

目的 观察小剂量马法兰治疗中、高危骨髓增生异常综合征(MDS)的疗效和药物不良反应.方法 共有按MDS国际预后积分系统(IPSS)判断为中、高危组的30例初治患者入组.治疗方案为:马法兰2 mg,口服,每日1次,直至病程进展所致全血细胞减少加剧或骨髓原始细胞比例增高停药.达完全缓解(CR)或部分缓解(PR)者继续用药直至病情复发停药.结果 按2006年MDS 国际工作组(IWG)疗效修订标准判定,CR 9例(30.0%),PR 3例(10.0%),骨髓缓解(MCR)加血液学进步(HI)3例(10.0%),MCR 1例(3.3%),病情稳定4例(13.3%),治疗失败10例(33.3%).总有效率66.7%.骨髓增生活跃及以下组患者的CR+PR率(60.0%)和总有效率(80.0%)明显高于骨髓增生明显活跃及以上组(分别为0%和40%)(P值分别为0.002和0.045).中位随访时间为15.5(1～52)个月,中位生存时间为18个月,中位无复发生存时间为11个月.治疗过程中3例患者出现轻度骨髓抑制,1例因血小板输注无效导致脑出血而死亡,未见其他明显药物不良反应.结论 小剂量马法兰是治疗中、高危MDS患者的一种安全、有效的方法,并且可能更适用于骨髓增生低下的患者.

Low-dose melphalan therapy for patients with intermediate- to high-risk myelodysplastic syndromes

Objective To observe the efficacy and side-effects of low-dose melphalan for the treat-ment of intermediate- to high-risk myelodysplastic syndromes(MDS) patients. Methods Thirty patients with intermediate- to high-risk MDS received oral melphalan at a daily dose of 2 mg. The melphalan therapy was continued until marrow blasts increased or severe cytopenia attributed to melphalan. Patients achieved com-plete remission(CR) or partial remission(PR) were still maintained with mclphalan until disease relapse. Results Among the 30 patients, 9 (30.0%) achieved CR, 3 (10.0%) PR, 3 (10.0%) bone marrow com-plete remission and hematology improvement(MCR + HI), 1 (3.3%) MCR, 4(13.3%) stable disease and 10(33.3%) no response, the overall response rate being 66.7% according to the Modified International Working Group Response Criteria for MDS. The CR plus PR rate (60. 0%) and total response rate (80.0%) in patients with normoeellular or hypocellular bone marrow were significantly higher than in those with hypercellular bone marrow (0.0% , 40%, respectively) (P =0.002 and 0. 045, respectively). Median overall survival(OS) and median relapse-free survival(RFS) were 18(95% CI 14-22)and 11 (95% CI 3-19)months, respectively. There was no side-effect except for slight marrow suppression in 3 patients and one patient died from brain hemorrhage on inefficacy of platelet transfusion. Conclusions Low-dose melphalan therapy for intermediate- to high-risk MDS patients is safe and effective, especially suitable for elderly patients with hypocellular marrow.