小剂量化疗药加与不加GM-CSF治疗高危MDS6例

小剂量化疗药加与不加ＧＭ－ＣＳＦ治疗高危ＭＤＳ６例赵文理候冰王歧山李梅生高危性骨髓增生异常综合征（ＭＤＳ）是指原始细胞增多，如不治疗终将转变为白血病的一组病例，主要包括分型中的ＭＤＳ－ＲＡＥＢ（难治性贫血伴原始细胞增多）及ＭＤＳ－ＲＡＥＢＴ（转变中的...     

骨髓增生异常综合症发病机制和临床治疗的研究进展

骨髓增生异常综合症（ＭＤＳ）发病的病理生理学机制尚不完全清楚,主要与ＭＤＳ的高度异常性有关。已知与ＭＤＳ发病相关的一些机制,如多种遗传学、表观遗传学、造血干细胞和造血微环境的异常等。随着对ＭＤＳ发病机制研究的进展,出现了一些新的治疗策略和新的治疗药物,作者拟就近年来有关新的进展作一介绍。     

柔红霉素－白蛋白药物微球的制备、特性及肿瘤实验治疗

为了提高化疗药物的治疗指数和降低其毒性，制备成柔红霉素－人血清白蛋白微球（Ｄａｕ－ＨＡ－ＭＳ）。绝大多数为单分散相微球，平均直径５６±１６μｍ，范围为２９～１９４μｍ，适用于导管动脉栓塞（ＴＡＥ）治疗。Ｄａｕ－ＨＡ－ＭＳ在生理盐水中能有效的释放Ｄａｕ，但无爆发释放的缺点。释放Ｄａｕ的光谱特性和体外细胞毒效应与原药相比无变化，表明Ｄａｕ通过微球制备仍保留原有的理化及生物学特性。实验表明，经腹腔注射Ｄａｕ－ＨＡ－ＭＳ使３０％的Ｓ－１８０腹水癌小鼠活存超过６个月，而肿瘤对照组及Ｄａｕ治疗组均分别在２１天和１４天全部死亡，说明Ｃａｕ－ＨＡ－ＭＳ有较好的疗效及较低的毒性。本结果提示，Ｄａｕ－ＨＡ－ＭＳ有可能用于人肝癌的ＴＡＥ治疗。     

荷S180肉瘤小鼠血中丙二醛和超氧化物歧化酶水平及蛇毒对其影响

目的：探讨荷Ｓ１８０肉瘤小鼠血中丙二醛（ｍａｌｏｎｄｉａｌｄｅｈｙｄｅ,ＭＤＡ）和超氧化的歧化酶（ｓｕｐｅｒｏｘｉｄｅ ｄｉｓｍｕｔａｓｅ,ＳＯＤ）的变化规律,以及采用中华眼镜蛇毒（ｎａｊａ ｎａｊａ ａｔｒａ ｖｅｎｏｍ,ＮＮＡＶ）进行治疗后对ＭＤＡ和ＳＯＤ的影响。方法：用ＴＢＡ比色法和放免均相竞争抑制法检测血中ＭＤＡ和ＳＯＤ－１,观察不同病期（种瘤后５天,１０天和１５天）荷瘤鼠血中ＭＤＡ和ＳＯ     

帕米膦酸二钠和^153Sm—EDTMP治疗骨继发性恶性肿瘤疗效对比 …

帕米膦酸二钠（ＡＰＤ）与＾１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物，为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和＾１５３Ｓｍ－ＥＤＴＭＰ组每组各２１例，结果显示：ＡＰＤ和＾１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ〉０．０５），ＡＰＤ与＾１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％，２３．８     

VlP与MVP方案治疗非小细胞肺癌的对照研究

目的：通过前瞻性对照研究,比较ＶＩＰ方案与ＭＶＰ方案治疗晚期非小细胞肺癌的疗效及不良反应。方法：共５３例晚期的非小肺癌患者随机入组,治疗应用ＶＩＰ方案（ＶＤＳ＋ＩＦＯ＋ＤＤＰ）,对照组应用ＭＶＰ方案（ＭＭＣ＋ＶＤＳ＋ＤＤＰ）,每例病人至少化疗２疗程。疗效及不良反应评价均按ＷＨＯ标准进行,每例病人随访生存期。结果：治疗组中１例ＣＲ,１５例ＰＲ,８例ＳＤ,１例ＰＤ,有效率（ＣＲ＋ＰＲ）为６４．０％;对     

^153Sm—乙二胺四亚甲基磷酸盐治疗骨肿瘤转移性疼痛

本文介绍了一种新的肿瘤转移性疼痛治疗方法－＾１５３Ｓｍ－乙二胺四亚甲基磷酸盐（＾１５３Ｓｍ－ＥＤＴＭＰ）放射药物治疗法。＾１５３Ｓｍ－ＥＤＴＭＰ血液清除快，病变区骨摄取高，对正常组织及造血系统的毒副作用小。经临床近千例验证，＾１５３Ｓｍ－ＥＤＴＭＰ对肿瘤转移性骨痛的缓解率为７６％～９６％，治疗后转移灶完全消失占１０％。＾１５３Ｓｍ－ＥＤＴＭＰ治疗是临床常规治疗无效后缓解及治疗转移性骨痛的首选方法。     

DA方案治疗老年人骨髓增生异常综合征完全缓解1例

ＤＡ方案治疗老年人骨髓增生异常综合征完全缓解１例徐燕丽老年人骨髓增生异常综合征（ＭＤＳ）发病率高，对老年人ＭＤＳ的治疗不是令人满意的，我院收治１例ＭＤＳ，用ＤＡ方案一疗程获完全缓解。报告如下。患者，女，６０岁，住院号５１０５００，因头昏乏力１月伴食欲...     

骨髓增生异常综合征相关性急性淋巴细胞性白血病（附7例报告）

目的：探讨骨髓增生异常综合征相关性急性淋巴细胞白血病（ＭＤＳ／ＡＬＬ）的特点。方法：ＭＤＳ／ＡＬＬ与骨髓增长综合征相关性急性髓细胞性白血病（ＭＤＳ／ＡＭＬ＿的临床及实验室特点进行比较,采用ｔ检验、检验统计。结果：ＭＤＳ转化成ＡＬＬ８．１４％,其类型为１型５例,３型２例。ＡＬＬ类型１例,Ｌ２６例。临床明在ＭＤＳ＝ＡＭＬ与ＭＤＳ／ＡＬＬ二组之间无明显差异。骨髓象二组之间差交大。ＭＤＳ／ＡＬＬ在ＭＤＳ期     

支气管动脉灌注顺铂和长春花碱酰胺治疗难治性局部进展期NSCLC

1994年 3月到 1996年 1月 ,我们采用支气管动脉灌注长春花碱酰胺 (ＶＤＳ)加顺铂 (ＤＤＰ)治疗对长春碱类加丝裂霉素 (ＭＭＣ)和ＤＤＰ全身化疗无效的 2 8例局部进展期非小细胞肺癌 (ＮＳＣＬＣ)患者 ,取得了满意的效果。现报告如下。1　材料与方法1.1　病例选择　患者均为对长春碱类 [长春花碱(ＶＬＢ)或ＶＤＳ或去甲长春花碱 (ＮＶＢ) ]加ＭＭＣ加ＤＤＰ联合化疗无效 ,即经过≥ 2个周期的化疗 ,评价时间距末次化疗 3～ 4周 ,疗效为稳定和进展者。患者经病理或细胞学证实为ＮＳＣＬＣ ,Ｋａｒｎｏｆｓｋｙ评分≥ 6 0分 ,治疗前肝、肾功能正…     

New agents in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myeloid leukemia (AML). Therapeutic interventions for MDS other than allogeneic stem cell transplantation have been palliative. Novel and targeted therapeutic agents such as the inhibition of farnesyltransferases and receptor tyrosine kinases, more potent thalidomide analogs, arsenic trioxide, immunomodulating agents, hypomethylating agents, and histone deacetylase inhibitors have shown encouraging results and may offer durable benefit to patients with MDS. Further development of rational therapies and improvements in the outcome of patients with MDS are likely to emerge from an increased understanding of the pathophysiology of these diseases.     

Epidemiology, natural history, and practice patterns of patients with myelodysplastic syndromes in 2010

The incidence rate of the myelodysplastic syndromes (MDS) in the United States is approximately 3.4 per 100,000 people, accounting for more than 10,000 new diagnoses annually and an estimated 60,000 people living with the disease. Common risk factors for developing MDS include advanced age, male gender, and antecedent exposure to chemotherapy or radiation as treatment for other cancers, which alone accounts for 10% of MDS cases. Patients with MDS typically are diagnosed when they are in their 70s, have significant cytopenias, and have substantive transfusion needs. Erythropoiesis stimulating agents are used by more than 50% of patients, although the use of disease-modifying agents is increasing, and may ultimately have an impact on the number of patients living with MDS.     

Management of Transfusion-Dependent Myelodysplastic Syndromes

The clinical and biological heterogeneity of the myelodysplastic syndromes (MDS) has engendered new expectations that therapy must be individualized. As a consequence, anemia management strategies for patients with MDS have evolved from a long-standing reliance upon supportive measures to active treatment guided by the risks posed by the disease. Median survival for a patient with MDS ranges from several months to ≥5 years with differing treatment goals, such as the promotion of hematopoiesis with recombinant cytokines to reducing the risk of leukemic transformation or death with agents such as azacitidine. As further insight into the molecular pathogenesis of these disorders has emerged, significant progress has been made in identifying new drug targets. Among these promising new agents are the farnesyl transferase inhibitors, immunosuppressive therapy, small-molecule tyrosine kinase inhibitors, and angiogenesis inhibitors. Phase I and II trials have shown encouraging activity with these agents and larger randomized trials are expected to define their place in the management of MDS.     

High-Risk Myelodysplastic Syndromes: Chemotherapy,Transplantation, and Beyond

Allogeneic hematopoietic cell transplantation (HCT) has curative potential for patients with myelodysplastic syndromes (MDS), though with considerable nonrelapse mortality and morbidity. The International Prognostic Scoring System, despite its confines, remains a widely used tool guiding treatment decisions in MDS. The two hypomethylating agents, 5-azacytidine (azacitidine) and 5-aza-2-deoxycytidine (decitabine), are both effective in high-risk MDS, but about 50% of high-risk MDS patients fail to achieve a meaningful response, and these agents offer only a modest survival benefit, with a median response duration of 13 months. The more recent proposed risk models of MDS, as well as modern transplant strategies and expanded alternative donor sources, have helped to increase the number of patients offered curative treatment. As both drug therapy and HCT modalities evolve, treatment decisions are certain to become more complex. Current therapeutic options should view the hypomethylating agents as a way to optimize disease response before (and possibly after) HCT.     

Treatment options in myelodysplastic syndromes: a new frontier

Myelodysplastic syndromes (MDS) are very heterogeneous diseases in terms of clinical presentation and prognosis. Patients with pure red cell dysplasias have a life expectancy of more than 10 years, whereas those with refractory anemias with excess blasts have survival shorter than 6 months. Until a few years ago, therapeutic options were palliative and supportive care only. Quite recently, the treatment panorama for MDS has radically changed and the different biological behavior of MDS requires a precise choice among completely different therapies: immunosuppressive agents, anti-apoptotic agents and growth factors are effective in low risk MDS, whereas epigenetic drugs, tyrosine kinase inhibitors, and possibly high dose chemotherapy and bone marrow transplantation are valuable in high risk MDS. We review the results of such therapies and the selection criteria for MDS patients.     

骨髓增生异常综合征患者低甲基化治疗失败后的治疗选择

骨髓增生异常综合征(MDS)的主要治疗包括支持治疗(如输血、集落刺激因子、螯合铁等)和靶向药物(5-氮杂胞苷、地西他滨、来那度胺).如果患者对以上药物无效,则缺乏有效的治疗方法.治疗失败后,目前努力的方向是继续调整并优化去甲基化药物(HMT)方案,改善药物制剂[口服制剂和(或)新制剂],根据突变筛选患者,提高HMT治疗MDS的针对性和有效性.此外,正在进行的研究重点是确定用来作为HMT治疗失败后挽救MDS患者的独特药物.如rigosertib最有可能使特定人群[原发性难治性和国际预后评分系统(IPSS)评分为高危的患者]受益.鉴于实体肿瘤免疫逃逸的重要进展,程序性死亡受体1(PD-1)和PD-1抑制剂单剂可在早期治疗和复发时联合HMT治疗MDS.对于那些有特定靶向突变基因的少数民族患者,有替代药物(IDH1/2)是非常有希望的.骨髓移植是治愈MDS的唯一方法,但因MDS进展时大多患者都年老体弱,所以移植的可行性不大.     

Treatment Options in Myelodysplastic Syndromes: A New Frontier

Abstract

Myelodysplastic syndromes (MDS) are very heterogeneous diseases in terms of clinical presentation and prognosis. Patients with pure red cell dysplasias have a life expectancy of more than 10 years, whereas those with refractory anemias with excess blasts have survival shorter than 6 months. Until a few years ago, therapeutic options were palliative and supportive care only. Quite recently, the treatment panorama for MDS has radically changed and the different biological behavior of MDS requires a precise choice among completely different therapies: immunosuppressive agents, antiapoptotic agents and growth factors are effective in low risk MDS, whereas epigenetic drugs, tyrosine kinase inhibitors, and possibly high dose chemotherapy and bone marrow transplantation are valuable in high risk MDS. We review the results of such therapies and the selection criteria for MDS patients.     

SOHO State of the Art & Next Questions: Myelodysplastic Syndromes: A New Decade

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell disorders. The 2020 Surveillance, Epidemiology, and End Results data demonstrates the incidence rate of MDS increases with age especially in those greater than 70 years of age. Risk stratification that impact prognosis, survival, and rate of acute myeloid leukemia (AML) transformation in MDS is largely dependent on revised International Prognostic Scoring System along with molecular genetic testing as a supplement. Low risk MDS typically have a more indolent disease course in which treatment is only initiated to ameliorate symptoms of cytopenias. In many, anemia is the most common cytopenia requiring treatment and erythroid stimulating agents, are considered first line. In contrast, high risk MDS tend to behave more aggressively for which treatment should be initiated rapidly with Hypomethylating Agents (HMA) being in the frontline. In those with high risk MDS and eligible, evaluation for allogeneic stem cell transplant should be considered as this is the only potential curative option for MDS. With the use of molecular genetic testing, a personalized approach to therapy in MDS has ensued. As the treatment landscape in MDS continues to flourish with novel targeted agents, we ambitiously seek to improve survival rates especially among the relapsed/refractory and transplant ineligible.     

骨髓增生异常综合征表观遗传学治疗进展

 表观遗传改变与基因改变有一个重要的区别就是表观遗传改变是可逆的,通过使用相应的表观遗传药物可使沉默的抑癌基因重新表达。骨髓增生异常综合征（MDS）的表观遗传治疗已经取得了很大的发展,当前应用于临床的表观遗传药物主要包括DNA去甲基化药物和去乙酰化酶抑制剂。得到FDA批准上市的DNA去甲基化药物5-氮杂胞苷和地西他滨均为MDS治疗药物,可作为中高危患者尤其是不能耐受化疗的老年患者重要的治疗选择;去乙酰化酶抑制剂如丙戊酸等目前在治疗MDS中大多处于I期临床试验阶段,可能在治疗低危MDS中有一定价值,但其剂量和治疗效果尚需进一步评估;去甲基化药物和去乙酰化抑制剂二者联用治疗MDS可能具有协同作用,但目前的临床试验尚不能证实其优于去甲基化药物的单用,仍需大样本的临床病例和合理的治疗方案来验证其安全有效性。     

Clinical use of erythropoietic stimulating agents in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias resulting from ineffective hemopoiesis. Anemia affects the vast majority of patients with MDS and contributes substantially to their symptoms. For more than 20 years, recombinant human erythropoietin has been available for clinical use, and it has been employed in an attempt to relieve MDS-related anemia. Erythropoietin-alpha, erythropoietin-beta, and more recently darbepoetin have been found to increase hemoglobin levels and abolish transfusion dependence in 19%-68% of MDS cases. This wide range in clinical response depends on several biological and clinical variables that allow the selection of patients with the highest probability of successful treatment. These agents are a mainstay in MDS therapy, but many issues are still open in terms of the initiation of therapy, the optimal dosage of erythropoietic stimulating agents (ESAs), the most efficient type of ESA, and the duration and outcome of such treatments. In this review, the mechanisms of response and predictive factors as well as an analysis of the clinical activity of ESAs in MDS therapy are presented.