骨髓增生异常综合征的治疗进展

骨髓增生异常综合征是一组造血干细胞克隆性疾病,因病态造血导致进行性、难治性血细胞减少为特征,临床主要表现为贫血、感染和出血。少数有进展为急性白血病的危险。目前仍缺乏有效的根治疗法,本文重点讨论MDS的现有治疗和相关的支持治疗。     

骨髓增生异常综合征的现代治疗

骨髓增生异常综合征（ＭＤＳ）是克隆性造血干细胞疾患,临床表现呈现多样性、异质性,以血细胞减少为其特征。少数有进展为急性白血病的危险。在既往１０年中出现了许多新的治疗,有些新药正在研发之中。本文复习讨论ＭＤＳ的分类和预后系统,重点复习ＭＤＳ的现有治疗和相关的支持治疗。     

低增生性骨髓增生异常综合征治疗的进展

 低增生性骨髓增生异常综合征（Hypo-MDS）骨髓结构紊乱，病态巨核细胞增生明显，以骨髓低细胞容积和病态造血为共同特征，目前尚无统一的治疗标准，对其治疗应该引起注意。文章对Hypo-MDS治疗的研究进展进行了综述。     

骨髓增生异常综合征的靶向治疗

骨髓增生异常综合征(myelodysplastic syndrone,MDS)是包括一组不同起源的造血干/祖细胞克隆性疾病,以无效造血和向急性白血病转化为特点.MDS的发展虽有近百年的历史,但对MDS的发生机制的认识仍然有限,阻碍了MDS治疗的发展.近年来,MDS发病机制的研究在分子生物学水平有了一些突破,出现了很多的靶点,许多针对这些靶点的新药相继出现并在临床试验中获得了令人鼓舞的成绩.各个试验的疗效标准各不相同,但与2000年国际工作组制定的判定标准基本统一.     

阿米福汀在骨髓增生异常综合征中的治疗作用

目的研究阿米福汀改善骨髓增生异常综合征(MDS)外周血细胞减少的疗效。方法对18例MDS应用阿米福汀治疗,观察疗效。结果18例患者中完全反应(completeresponse,CR)3例(16.67%),部分反应(partialresponse,PR)7例(38.89%),总反应率为55.56%。结论阿米福汀在治疗MDS方面有一定的作用。     

高危骨髓增生异常综合征的治疗

骨髓增生异常综合征（MDS）是一类造血干细胞恶性克隆性疾病,其治疗主要集中在表观遗传学治疗、化疗、干细胞移植以及新药方面,现将各种治疗方法进行综述。     

骨髓增生异常综合征非细胞毒治疗现状

骨髓增生异常综合征(MDS)是一组并不少见的异质性多能造血干细胞克隆性疾病,主要特点为骨髓造血细胞分化成熟障碍、无效造血、正常造血功能减退,常伴血细胞机能异常,有向白血病转化的倾向.MDS的治疗,大致可分为二大类,即:细胞毒(cytotoxic)治疗与非细胞毒(non-cytotoxic)治疗.     

骨髓增生异常综合征临床研究进展

 主要介绍骨髓增生异常综合征（MDS）与自身免疫现象或疾病的发病机制,MDS与再生障碍性贫血、MDS与阵发性睡眠性血红蛋白尿症（PNH）之间的关系及MDS靶向治疗的一些研究进展。     

The burden of autoimmunity in myelodysplastic syndromes

The clinical history of patients with myelodysplastic syndromes (MDS) is characterised by bone marrow insufficiency as well as by the possible evolution into acute leukaemia. However a number of reports highlight the frequent occurrence of autoimmune manifestations involving different sites and organs. The present review will first describe the clinical pictures most often observed in MDS patients. The actual burden of autoimmunity will be then addressed by focusing on the few available registry studies. Finally, the potential collateral impact of specific treatments for MDS on the evolution of autoimmune disorders will be considered.     

低剂量地西他滨治疗骨髓增生异常综合征的疗效分析

目的:观察低剂量地西他滨治疗骨髓增生异常综合征(MDS)的疗效及安全性。方法:9例骨髓增生异常综合征患者应用地西他滨20mg/m2.d,静脉滴注,持续时间大于1小时,连续5天,至少连续2疗程,观察MDS患者病程的改变、生存质量和血液学指标等。依据NCICTCAE标准判断药物不良反应。结果:1例CR、1例PR、2例获得血液学改善,输血频次减少;上述4例治疗有反应的MDS患者均在随访中,目前尚未转为急性白血病;5例患者疾病进展,2周期治疗后,输血频次无明显减少,复查骨髓细胞学呈低增生性,且原始细胞比例较治疗前无明显下降,其中有2例MDS-RAEB 2 IPSS评分为高危患者原始细胞比例明显升高,短期内转化为急性髓性白血病。结论:低剂量地西他滨与其他强烈化疗方案相比,安全性强,化疗相关死亡率低,不良反应易于处理。     

Diagnostic flow cytometry for low-grade myelodysplastic syndromes

It has long been considered that flow cytometry (FCM) has little role in clinical practice in the diagnosis of myelodysplastic syndromes (MDS). However, recent advances in the analytical method and knowledge of MDS FCM are changing this stereotype. This paper reviews the concept and current status of FCM in the diagnosis of low-grade MDS. The diagnosis of low-grade MDS in the absence of ringed sideroblasts and chromosomal aberration is not always straightforward, and a report from a recent international working conference has proposed FCM as an adjunctive diagnostic test for such cases. Currently, only a limited number of laboratories are applying FCM to the diagnosis of MDS. Furthermore, standard analytical methods in FCM for MDS have not been established, and no single FCM parameter is sufficiently sensitive and specific to make the diagnosis of MDS. To establish MDS FCM as a widely accepted, dependable diagnostic tool, prospective studies should increase flow parameters that can be analysed reproducibly and determine their sensitivity and specificity, either alone or in combination. CD34+ cell-related parameters that are applicable for diagnosing low-grade MDS in many laboratories are introduced here.     

骨髓增生异常综合征剪接体突变的研究进展

研究发现剪接体突变在骨髓增生异常综合征(myelodysplastic syndrome,MDS)疾病的发生发展中发挥重要作用,其突变基因包括SF3B1、U2AF1(U2AF35)、SRSF2、ZRSR2、PRPF40B、SF1、SF3A1和U2AF2等,突变基因(45%~85%)发生在mRNA剪接过程中的3'剪接位点,主要表现为杂合性错义突变。了解RNA剪接对MDS的靶向治疗及预后具有指导作用。本文就剪接体相关突变基因在MDS中的致病机制、靶向治疗及临床预后等进行综述。      

Increased proliferation of eosinophil clusters in myelodysplastic syndromes

A patient with myelodysplastic syndromes (MDS) developed eosinophilia during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). To study the mechanism of this eosinophilia, we investigated the proliferation of eosinophil colony-forming units (CFU-Eo) in nine patients and four healthy controls. Eosinophil clusters increased significantly in the patients (P < 0.01) compared with controls, but eosinophil colonies were not different between controls and MDS patients. In addition, the eosinophil clusters were significantly increased with rhGM-CSF in MDS patients compared with controls, although serum GM-CSF concentrations were similar in both groups. These results suggest that eosinophil clusters are increased in MDS either through abnormal progenitor proliferation or hypersensitivity to GM-CSF.     

Risk factors for myelodysplastic syndromes: a case-control study in Greece

Objective: The etiology of most cases of myelodysplastic syndromes (MDS) has not been elucidated. We have undertaken an investigation in Greece to determine the risk profile of adult de-novo MDS. Methods: A case–control investigation was conducted in a large Veterans' hospital over a five-year period, covering 84 MDS cases and 84 age- and gender-matched controls with minor non-neoplastic non-infectious conditions from the same study base. Cases and controls reported to the medically trained principal investigator lifestyle characteristics and medical histories, with emphasis on autoimmune disorders and allergic conditions. Results: Alcohol intake and tobacco smoking jointly increased significantly the risk of MDS (odd ratio contrasting ever smokers and regular drinkers of at least one glass per day to never smokers and drinkers of less than one glass per day: 9.54, 95% CI 3.52–25.82) whereas each of these factors alone had limited effect. There was also evidence that autoimmune conditions, but not allergic disorders, were positively associated with MDS risk, irrespective of their occurrence during the recent (less than ten years) or the remote (more than ten years) past (OR 3.34, 95% CI 1.15–9.74; OR 3.50, 95% CI 1.19–10.26, respectively). Conclusion: We found evidence that both exogenous and endogenous factors may play a role in the etiology of the so-called de novo myelodysplastic syndromes, but these findings need further confirmation.     

骨髓增生异常综合征去甲基化治疗的研究新进展*

表观遗传学异常是骨髓增生异常综合征（myelodysplastic syndromes,MDS ）发病的重要机制之一,DNA 甲基化异常是MDS 最常见的表观遗传学改变。抑制DNA 异常甲基化可以改善部分MDS 患者的病情,延长其生存期。目前被批准用于MDS 临床治疗的去甲基化药物主要有阿扎胞苷和地西他滨,这两种药物在MDS 患者中均显示出一定的疗效。本文对该药的应用及进展研究进行综述。     

Pulmonary infections in patients with myelodysplastic syndromes receiving frontline azacytidine treatment

Pulmonary infections (PIs) are a major complication of patients with myelodysplastic syndromes (MDS). We retrospectively evaluated 234 MDS patients treated with azacytidine (AZA). The total number of AZA cycles was 2886 (median 8 cycles per patient). There were 111 episodes of PI (3.8% of AZA cycles) in 81 patients (34.6%). PIs were considered of fungal origin in 27 cases (24.3%), associated to bacteremia in 11 cases (9.9%), to influenza infection in two cases (1.8%) and of unknown origin in the remaining 71 cases (64.0%). Forty-five PI episodes were documented in cycles 1 to 4 of AZA (5.1% of 875 cycles) and the remaining 66 episodes beyond the fourth cycle (3.2% of 2011 cycles) (P = .017). Overall, a fungal PI was documented in 13/875 (1.5%) cycles 1 to 4 and in 13/2011 (0.6%) cycles beyond the fourth cycle (P = .001). A baseline chronic pulmonary disease was significantly associated to a higher risk of severe PIs. In the survival analysis, cases of PI in patients who progressed to acute leukemia (PAL) were excluded, in view of the predominant influence of PAL on the outcome of the patients. A PI unrelated to PAL documented during the first 4 AZA cycles was an independent factor predicting lower survival (OR, 2.13; 95% CI, 1.37-3.33; P = .001). In conclusion, PIs are common in MDS patients receiving AZA, in particular during the first cycles of treatment and are associated with an unfavorable outcome. The results of our study raise the issue of the need of a tailored infection prevention strategy.     

沙利度胺联合十一酸睾酮和维甲酸治疗低危骨髓增生异常综合征

目的观察沙利度胺联合十一酸睾酮和维甲酸治疗低危骨髓增生异常综合症(MDS)的疗效和不良反应。方法49例低危MDS患者均为难治性贫血(RA),分为两组,A组使用十一酸睾酮和维甲酸,B组除该两种药物外还联合使用沙利度胺。比较两组的疗效,观察沙利度胺的副反应。结果A组总有效率为39.1%,缓解率为26.1%;B组总有效率为75.0%,缓解率为54.2%,两者均有显著差异(P<0.05)。A组血红蛋白(Hb)增加大于30g/L的平均时间为135.9±23.7天,B组为93.8±33.5天,差异非常显著(P<0.005)。A组平均红细胞输注量为18.1±8.0单位,B组为10.6±7.0单位,差异也有显著性(P<0.005)。沙利度胺的主要不良反应是嗜睡、便秘和水肿。结论沙利度胺联合十一酸睾酮和维甲酸治疗低危MDS优于仅用十一酸睾酮和维甲酸,且毒副作用小,值得临床推广使用。