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。     

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。     

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58例临床分析

骨髓增生异常综合征(myelodysplastic syndrome,MDS)是一种源于多能造血干细胞的恶性克隆性疾病,现将我院1994年6月-2000年4月收治的58例MDS分析报道如下.     

小剂量地西他滨治疗中高危骨髓增生异常综合征的Meta分析

目的 系统评价小剂量地西他滨治疗中高危骨髓增生异常综合征（MDS）疗效和安全性。方法 计算机检索PubMed、Cochrane Library、Embase、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）1995-2012年间发表的关于小剂量地西他滨治疗MDS的文献资料。并纳入随机对照试验（RCT）,采用Review manager5.0软件进行Meta分析。结果 共纳入3篇随机对照试验（RCT）,共894例患者。Meta分析结果显示,地西他滨与支持治疗相比,总生存率（OR）[OR=22.9,95%CI(7.51,69.85),P＜0.00001]、部分缓解率(PR) [OR=17.23,95%CI(2.27,130.76),P=0.006]、血液学改善（HI）[OR=3.21,95%CI(1.53,6.75),P=0.002]、中位生存期（MST）[13.5月 vs. 7.3月,P＜0.05]、Ⅲ/Ⅳ级发热伴中性粒细胞减少[OR=4.85,95%CI(2.55,9.21),P＜0.00001] 差异有统计学意义。完全缓解率（CR）[OR=6.39,95%CI(0.25,166.49),P=0.26] 、Ⅲ/Ⅳ级血小板减少症[OR=2.35,95%CI(0.63,8.69),P=0.20]差异无统计学意义。结论 小剂量地西他滨可提高骨髓增生异常综合征患者总体生存率和部分缓解率,有助于血液学改善。但是增加Ⅲ/Ⅳ级中性粒细胞减少症的发生,部分患者也会出现血小板减少症、恶心呕吐、腹泻等不良反应。     

Clinical and Biological Effects of Erythropoietin treatment of Myelodysplastic Syndrome

To evaluate its clinical efficacy as well as its biologic safety, human recombinant Erythropoietin (rh-Epo) was given to 19 patients with myelodysplastic syndromes (MDS) in an open non-randomized study. Among the seventeen evaluable patients only two showed an apparent hematologic response to rh-Epo treatment. In these patients hemoglobin levels increased from a mean pretreatment value of 8.5 and 8.4g/dl up to 11.7 and 11.3 g/dl respectively and remained relatively stable for several weeks. In one of these patients the transfusion requirement decreased from 4 to 1.5 units per month whereas the other had no transfusion requirement during the whole period of rh-Epo treatment. Interestingly, when the responding patients, after a “wash-out” period of at least ten weeks, received an additional course of rh-Epo results were less impressive. Before treatment the serum level of endogenous Epo was 18 and llOmU/ml in the two responding patients, whereas a mean value of 532 mU/ml (range 17-2797 mU/ml) was observed in non responders. The treatment of MDS patients with rh-Epo was clinically well tolerated since no relavent side effects were registered. Moreover, no evidence of harmful cytogenetic changes nor activation of myeloid growth factor genes, as determined by Northern blot analysis of GM-CSF and G-CSF gene expression, could be related to rh-Epo treatment. Overall, it appears that administration of rh-Epo is well tolerated but the therapeutic effects appear to be restricted to a minority of patients and a limited period of time.     

Copper and Zinc Levels in Myelodysplastic Syndrome Patients versus Healthy Subjects

Background: Myelodysplastic syndrome (MDS) is a heterogeneous hematological disease and certain serum factors are assumed to be involved in its pathogenesis and progression. Given this, our aim was to comparatively investigate the copper, zinc, and iron levels in MDS patients and healthy individuals. Methods: This case-control study was conducted on 31 patients with MDS (according to the WHO criteria after investigating laboratory tests such as peripheral blood smear and bone marrow aspiration) attending Bahonar Hospital, Kerman, Iran, and 31 healthy subjects from 2016 to 2018. The levels of copper, ceruloplasmin, zinc, ferritin, and iron were compared between the two groups. Results: Among the MDS patients, five individuals (16.13%) had low serum copper level (mean: 67.8 ± 4.35 µg/dl). Serum copper level was 111.3 ± 27.7 and 138.3 ± 26.6 in case and control groups, respectively (P = 0.0001). The serum zinc level and bone marrow iron level were also significantly different between the two groups (P < 0.05). Conclusion: Overall, it can be concluded that because only a small proportion of the MDS patients enrolled in this study were found to have lower copper levels compared with the MDS patients population, further studies with a larger sample size and also clinical trials in MDS patients with serum zinc, and copper deficiency are recommended, and post-treatment hematological reassessment would also be beneficial to achieving more definitive results.     

减量HA方案和ATRA治疗高危骨髓增生异常综合征20例

目的：观察减量的三尖杉酯碱（H），阿糖胞苷（A）和全反式维甲酸（ATRA）诱导治疗高危骨髓增生异常综合征的疗效。方法：对20例高危骨髓增生异常综合征患者，应用三尖杉酯碱2－3mg／天，静脉滴注，连用5天，阿糖胞苷100mg/天，静脉滴注，连用5天，ATRA30－60mg/天，分次口服，结果：完全缓解（CR）6例（30％），部分缓解3例（15％），无效11例（55％），7例（35％）在治疗中转化为急性白血病，化疗相关性死亡3例（15％），结论：减量HA方案和全反式维甲酸治疗高危MDS有明显疗效，但老年患者治疗相关性死亡率较高，需注意个体化治疗。     

Clinical Outcomes of Decitabine Treatment for Patients With Lower-Risk Myelodysplastic Syndrome on the Basis of the International Prognostic Scoring System

IntroductionDecitabine has shown clinical benefits in patients with intermediate (INT)-2 or high-risk myelodysplastic syndrome (MDS), determined according to the International Prognostic Scoring System (IPSS), but the benefits have not been well demonstrated in patients with lower-risk (IPSS low or INT-1) disease. Recently, it was proposed that the prognosis for patients with IPSS lower-risk disease is heterogeneous, with a substantial proportion of these patients having poor survival.Patients and MethodsThis study included patients with IPSS lower-risk MDS from the DRAMA (An Observational Study for Dacogen Long-Term Treatment in Patients With Myelodysplastic Syndrome; NCT01400633) and DIVA (A Study for Dacogen Treatment in Patients With Myelodysplastic Syndrome; NCT01041846) studies, which were prospective observational studies on the efficacy and safety of decitabine treatment in patients with MDS. Using the Lower-Risk Prognostic Scoring System [LR-PSS], we classified IPSS lower-risk MDS. Patients in each LR-PSS category were divided according to overall response (OR) to decitabine treatment, and survival outcomes were compared.ResultsOne hundred sixteen patients were enrolled: LR-PSS category 1 (n = 12; 10.3%), category 2 (n = 56; 48.3%), and category 3 (n = 48; 41.4%). Survival outcomes differed among the 3 categories (P = .046). The overall survival according to OR showed a significant difference in total patients (P = .008) and category 3 patients (P = .003). We analyzed predictive factors for OR, but no variable was found to significantly affect OR.ConclusionDecitabine treatment showed a survival benefit in the higher-risk group of IPSS lower-risk MDS patients who responded to treatment, and classification using the LR-PSS category was helpful for this subgroup, indicating that decitabine treatment might alter the natural course of disease in these patients.     

Immunological Findings in Patients with Myelodysplastic Syndrome

Activation of monocytes and granulocytes in vitro by cytokines, in vivo administration of cytokines, as well as in vivo cytokine production due to infectious and inflammatory diseases causes changes of the surface expression density of certain membrane molecules. In recent studies we attempted to determine the feasibility of using flow cytometric immunophenotyping as a tool to develop a sensitive parameter for detecting infections at an early stage of disease when clinical parameters are still negative. Since infections are an important factor determining the clinical course of myelodysplastic syndromes (MDS), early detection of infection might be beneficial for these immunocompromised patients. We indeed found activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes of clinically infection free MDS patients suggesting enhanced immune activity in these patients, most likely due to latent or beginning infections. In particular, analyses of the expression density of receptors for IgG (Fc-γRs), complement receptors, and certain activation-associated surface molecules such as the CD67 and the M5 molecule seem to be of clinical relevance. We will also discuss findings concerning changes of cytokine levels and functional alterations of immunologic parameters in MDS patients.     

The Frequency of SF3B1 Mutations in Thai Patients with Myelodysplastic Syndrome

Genetic mutations in genes encoding critical component of RNA splicing machinery including SF3B1 are frequentlyidentified and recognized as the pathogenesis in the development of myelodysplatic syndrome (MDS). In this study,PCR sequencings specific for SF3B1 exon 13, 14, 15, and 16 were performed to analyse genomic DNA isolated frombone marrow samples of 72 newly diagnosed MDS patients. We found that 10 of 72 (14%) patients harbor SF3B1missense mutations including E622D (1/72), R625C/G (2/72), H662Q (1/72), K666T (1/72), K700E (4/72) and G740E(1/72), respectively. Mutations were predominantly located on exon 14 and 15 of SF3B1 coding sequence. Interestingly,patients with SF3B1 mutations exhibited higher platelet counts (195×109/L VS. 140×109/L, p-value = 0.025) as well aslower hemoglobin levels (81 g/L VS. 92 g/L, p-value = 0.009) and associated with ring sideroblast phenotype (p-value< 0.001) when compared with patients without the SF3B1 mutation. In summary, we reported the frequency of SF3B1mutations in Thai patients with different subtypes of MDS. SF3B1 mutations were predominantly occurred in MDS-RSand considered as favourable prognosis value. This study further highlighted the clinical important of SF3B1 mutationsanalysis for the classification of MDS.     

A Pilot Trial of Lirilumab With or Without Azacitidine for Patients With Myelodysplastic Syndrome

Background

Enhancement of natural killer cell activity by blocking interactions between killer immunoglobulin (Ig)-like receptors (KIRs) and human leukocyte antigen-C (HLA-C) molecules can improve outcomes in myeloid malignancies. Lirilumab is a human IgG4 monoclonal antibody that blocks KIR/HLA-C interaction. We designed a study to evaluate the safety and efficacy of lirilumab as a single agent and in combination with azacitidine in patients with myelodysplastic syndrome (MDS).