Wijermans P W, Lübbert M, Verhoef G, Klimek V, Bosly A
Department of Haematology, Leyenburg Hospital, The Hague, The Netherlands.
Ann Hematol. 2005 Dec;84 Suppl 1:9-17. doi: 10.1007/s00277-005-0012-1.
During the last 10 years, three European phase II studies were performed to investigate the treatment of elderly patients with myelodysplastic syndrome (MDS) with low-dose 5-aza-2'-deoxycytidine (decitabine, DAC). All these European trial data were reviewed on the basis of the International Prognostic Scoring System (IPSS) risk criteria and the response criteria as recently published by an international working group. To investigate the results in a larger cohort of patients and to determine risk factors, all data were pooled with some observations from the PCH 95-06 US phase II study. The response rate in the 177 patients evaluated (median age 70 years) was 49%. The median response duration was 36 weeks, and the median survival was 15 months. Analysis of the data according to sex, age, French-American-British classification, percentage of blasts in the bone marrow, IPSS risk group, lactate dehydrogenase and cytogenetics did not reveal any factor predictive of response. Overall, 69% of patients benefited, including those with stable disease during therapy. Response duration was significantly shorter with increasing risk (according to the IPSS classification). Haemoglobin level and neutrophil count showed an inverse correlation to the IPSS classification. Univariate analysis showed a significantly inferior survival for elderly patients (>75 years of age) and for those with high levels of serum lactate dehydrogenase (LDH) (more than two times the normal values). Patients with high-risk cytogenetic abnormalities according to the IPSS risk criteria showed better overall survival than those with intermediate-risk abnormalities. When analysed according to the IPSS risk classification, high-risk patients had worse survival prospects following decitabine therapy than those with intermediate risk; however, compared to the originally reported IPPS outcomes for high-risk patients, they probably showed better survival. During the treatment period, 18% of the patients progressed towards acute leukaemia. Decitabine showed a rather low toxicity profile in this elderly patient group. In conclusion, low-dose decitabine is an active drug for the treatment of MDS patients, even for those older than 75 years with bad prognostic characteristics.
在过去10年中，开展了三项欧洲II期研究，以调查低剂量5-氮杂-2'-脱氧胞苷（地西他滨，DAC）治疗老年骨髓增生异常综合征（MDS）患者的疗效。所有这些欧洲试验数据均根据国际预后评分系统（IPSS）风险标准和国际工作组最近公布的缓解标准进行了审查。为了在更大的患者队列中研究结果并确定风险因素，所有数据与美国PCH 95-06 II期研究的一些观察结果进行了汇总。177例接受评估的患者（中位年龄70岁）的缓解率为49%。中位缓解持续时间为36周，中位生存期为15个月。根据性别、年龄、法美英分类、骨髓原始细胞百分比、IPSS风险组、乳酸脱氢酶和细胞遗传学对数据进行分析，未发现任何预测缓解的因素。总体而言，69%的患者从中获益，包括治疗期间病情稳定的患者。随着风险增加（根据IPSS分类），缓解持续时间显著缩短。血红蛋白水平和中性粒细胞计数与IPSS分类呈负相关。单因素分析显示，老年患者（>75岁）和血清乳酸脱氢酶（LDH）水平高（超过正常值两倍）的患者生存期明显较差。根据IPSS风险标准，具有高危细胞遗传学异常的患者总体生存期优于具有中危异常的患者。根据IPSS风险分类进行分析时，高危患者在地西他滨治疗后的生存前景比中危患者差；然而，与最初报告的高危患者IPPS结果相比，他们的生存期可能更好。在治疗期间，18%的患者进展为急性白血病。地西他滨在该老年患者组中显示出相当低的毒性特征。总之，低剂量地西他滨是治疗MDS患者的一种有效药物，即使对于那些预后特征不良的75岁以上患者也是如此。
