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急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)是一组生物学及预后不同的异质性疾病。近年来,分子生物学研究的进展为临床上根据细胞表型和遗传学特征更为准确地做出诊断,识别预后不同的亚型,根据其危险度调整治疗策略,使治疗更加个体化和高效低毒等提供了依据。本文综合近年来文献,就ALL的规范化诊治作一概述。1急性淋巴细胞白血病的诊断ALL的诊断应以细胞形态学、免疫表型以及细胞遗传学为基础,ALL亚型的确定直接与治疗方案的选择以及治疗反应和疾病预后密切相关。形态学是确立急性白血病诊断的主要依据。根据世界卫生组织(…     

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慢性髓性白血病(chronic myelogenous leukemia,CML)是以粒系增生为主,伴有特征性遗传学标志Ph染色体的骨髓增殖性疾病(MPD)。Ph染色体是9号和22号染色体断裂后交互易位的结果,导致ABL与BCR基因序列融合,进而产生一段210ku具有酪氨酸激酶活性的融合蛋白(P210BCR-ABL),该蛋白使信号传导途径异常激活,下游信号持续磷酸化,MYC和BCL-2转录增加,导致造血干细胞增殖失控,凋亡受阻,粘附功能缺陷,细胞发生恶性转化。推测恶变发生在骨髓多能干细胞阶段。CML年发病率(1~1.5)/10万。各年龄均可发病,中位年龄50~60岁。病程分为相对缓和的慢…     

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急性髓性白血病(AML)是最常见的血液系统恶性肿瘤.由于人口老龄化,AML发生率呈上升趋势,同时淋巴瘤、肉瘤、乳腺和睾丸肿瘤等经治疗存活的患者增多,其治疗相关骨髓增生异常综合征(MDS)、AML发生率亦逐渐上升.近年来,AML的诊断、分类标准以及治疗模式有了较多变化,并在某些领域取得了较大进展,通过联合化疗,5年无病存活率已达到30%,急性早幼粒细胞白血病的治疗更取得了可喜的突破,但老年白血病、继发性白血病的治疗仍不尽如人意.     

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再生障碍性贫血(aplastic anemia,AA)是一组不同病因引起的机体造血功能衰竭综合征,以骨髓造血红髓容量减少和外周血全血细胞减少为特征.患者临床表现为贫血、出血和感染,但发病缓急、病情轻重又不全相同.临床上,全血细胞减少的患者应考虑AA的可能,进一步行骨髓穿刺和骨髓活检常可确诊.     

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特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)是一种获得性自身免疫性疾病,是由于人体内产生抗血小板自身抗体导致网状内皮系统破坏血小板过多从而造成血小板减少[1].该病的年发病率为(50～100)/106,其中半数以上是儿童.     

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骨髓增生异常综合征(MDS)是一组起源于造血干细胞的克隆性疾病,其特征性病理生理改变是克隆性造血干细胞和(或)祖细胞发育异常(dysplasia)及无效造血(inef-fective hematopoiesis),其临床特征表现为主要发生于高龄人群的不明原因的慢性进行性血细胞减少(绝大多数为全血细胞减少)、骨髓造血细胞增多或正常,有发育异常的形态学改变,病程中常易发生致死性感染和出血,其转变为急性髓性白血病(AML)的危险性很高[1]。MDS分型已由FAB分型标准过渡到WHO分类系统标准[2-3]。最近几年,国际上推出了依据循证原则制订的各种血液病临床实践指南,其…     

798例M蛋白阳性患者的临床分析

目的通过对798例M蛋白阳性病例的分析,提高对这类疾病的认识,减少误诊和漏诊。方法分析M蛋白阳性患者的病种分布与年龄、性别的关系,多发性骨髓瘤（MM）与非MM首发症状的比较,以及MM各型免疫球蛋白含量的差异与非MM患者M蛋白的特点。结果M蛋白阳性的病例中,MM648例（81.2%）,华氏巨球蛋白血症（WM）34例（4.3%）,良性或继发性单克隆免疫球蛋白疾病116例（14.5%）。患者平均年龄58.3岁,男、女性别病种分布无差异性。MM首发症状以腰酸、骨痛为主,非MM则以发热、纳差、乏力为主,二者差异具有显著性。MM中IgG型290例（44.8%）,IgA型143例（22.1%）,轻链型138例（21.3%）,IgD型45例（6.9%）,非分泌型30例（4.6%）,双克隆型2例（0.3%）。除IgD型外,各型中κ和λ比较差异无显著性。良性或继发性单克隆免疫球蛋白升高者平均M蛋白含量（11.3±6.5）g/L,其中意义未明的单克隆免疫球蛋白血症（MGUS）55例,占M蛋白阳性患者的6.9%;非霍奇金淋巴瘤（NHL）35例,占4.4%。结论M蛋白阳性主要见于MM。此外,尚可见于MGUS、NHL、WM等多种疾病。     

单克隆丙种球蛋白血症639例临床观察分析

目的了解M蛋白的分型及临床意义,提高认识和诊断水平。方法通过对1998年1月至2005年12月上海交通大学医学院附属新华医院血液科诊治及少量外院送检标本M蛋白阳性者共639例结合临床对年龄、性别和疾病分布,以及多发性骨髓瘤(MM)与意义未明或继发性单克隆丙种球蛋白(MGUS)的特点进行分析。结果639例M蛋白血症中IgG型409例(64.0%)、IgA型80例(12.5%)、IgM型79例(12.4%)、IgD型4例(0.6%)、轻链型27例(4.2%,其中κ9例、λ18例)、双克隆型27例(4.2%)、单克隆型13例(2.0%)。该组患者病种分布,MM115例(18.0%)、华氏巨球蛋白血症(WM)13例(2.0%)、肾原发性淀粉样变性(AL)1例、非霍奇金淋巴瘤(NHL)19例(3.0%)、慢性淋巴细胞白血病(CLL)5例(0.8%)、MGUS473例(74.0%)、寡克隆13例(2.0%)。结论M蛋白血症是一种亚临床现象,主要见于MM及淋巴细胞增殖性疾病,意义未明或继发者检出率有增加趋势。     

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目前,多发性骨髓瘤(MM)是一种不可治愈的、慢性进展的恶性肿瘤,约占所有恶性血液肿瘤的10%,其在西方国家,年龄调整后发病率为2.5/10万～7.2/10万。近年来,在MM的早期诊断方法、临床分期、治疗和疗效评价等方面都取得了重大进展。本文将就以上这几个方面做一论述。1多发性骨髓瘤的诊断血清游离轻链(FLC)检测是一种检测体内是否存在克隆性浆细胞的高度敏感的检测方法。该检测通过免疫比浊法分别测定出血清中的游离轻链(未与重链结合成完整免疫球蛋白的轻链)κ和λ的量,并计算出κ/λ。κ/λ的正常值范围为0.26～1.65,如果比值低于0.26或高…     

肺耐药蛋白基因在多发性骨髓瘤中的表达及意义

到目前为止 ,多发性骨髓瘤 (MM )的治疗仍以化疗为主 ,但是治疗效果并无质的飞跃 ,多药耐药的产生可能是一条重要的原因 ,肺耐药相关蛋白 (LRP)基因于 1995年被克隆并定位 ,我们用半定量逆转录 -聚合酶链反应 (RT PCR)方法检测了 4 1例MM患者LRP基因的表达 ,探讨其表达与化疗反应及预后的关系 ,旨在进一步研究MM的耐药机制 ,指导其治疗。一、资料与方法1.对象 :所有标本均收集自 1998年 1月 1日～ 2 0 0 0年5月 1日青岛医学院附属医院门诊及住院患者 ,其中初治MM 2 1例 ,男 13例 ,女 8例 ,年龄 2 8～ 78岁 ;复治MM 2 0例 ,男 10例 …     

New treatment strategies for multiple myeloma

During the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high-dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high-dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non-cross-resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early relapse.     

Current treatment strategies for multiple myeloma

Until 1990, the melphalan-prednisone regimen was the standard treatment for multiple myeloma (MM). The role of alpha-interferon still remains controversial, both in induction therapy and in maintenance therapy. Over the last 10 years, there has been considerable improvement in the treatment of MM. In patients under 65 years of age, high-dose therapy with autografting has clearly demonstrated an advantage over conventional treatment. Bisphosphonates have proved very useful in reducing skeletal events. More recently, an old drug, thalidomide, has shown surprising efficacy in patients with advanced MM. Future trends include the extension of high-dose therapy to older patients and the use of immunotherapy in induction and/or maintenance therapy.     

多发性骨髓瘤治疗新药及新的治疗策略

从1962年以来,多发性骨髓瘤（Multiple Myeloma,MM）常规化疗方案多采用口服马法兰联用泼尼松（MP）,其后也应用VAD,M2等改良方案,但完全缓解率不到5%,中位生存期不超过3年,MM病人从治疗中获益有限.近10年来,随着临床认识的深入,新的治疗药物不断涌现,由此衍生出一些新的治疗策略大大提高了治疗缓解率,使MM患者的生存期不断延长,甚至有治愈可能。     

雄黄在多发性骨髓瘤治疗中的作用

目的 :研究雄黄治疗多发性骨髓瘤 (MM )的作用机制 ,并对其临床效果进行观察。方法 :采用MTT法、双抗体夹心ELISA法检测 15例MM患者应用雄黄治疗前后血清中白细胞介素 6 (IL 6 )活性及其受体 (sIL 6R)水平。结果 :MM患者血清中IL 6活性及sIL 6R水平明显高于健康对照组 (P <0 .0 1) ;应用雄黄治疗 5 0天后 ,MM患者血清中IL 6活性及sIL 6R水平无明显降低 (P >0 .0 5 ) ,Ⅲ期MM患者的IL 6活性显著高于Ⅰ、Ⅱ期 (P <0 .0 5 ) ,但sIL 6R水平两者差异无显著性意义 (P >0 .0 5 )。用雄黄治疗 15例患者 ,3例完全缓解 ,5例有效 ,7例无效。结论 :雄黄可能不是通过降低IL 6活性及sIL 6R水平来抑制肿瘤细胞生长的。     

Frontline treatment of multiple myeloma

The treatment of myeloma has been revolutionized by the availability of new drugs. Combination therapy followed by stem cell transplant holds the promise of ultimately curing a fraction of patients. Objective responses are the norm for induction therapy and up to 50% of patients achieve a complete remission. Ongoing clinical trials continue to address the role of long term maintenance therapy. Understanding the proper management of these agents is paramount to providing patients disease control and yet minimizing side effects from treatment.     

Thalidomide treatment in multiple myeloma

Thalidomide was first evaluated in patients with refractory multiple myeloma in the mid-90s. Based on the promising results achieved in these patients, the drug was subsequently used in earlier stages of the disease. Meanwhile, numerous phase II studies have been published using different doses and treatment schedules of thalidomide. In order to enhance efficacy, combinations of thalidomide with dexamethasone, chemotherapy and interferon were tried in different settings. In these trials important data regarding the toxicity profile of thalidomide have also been collected. Several trials in newly diagnosed myeloma patients are still ongoing. In the future, the optimal dose of thalidomide and the best schedule in combination with dexamethasone or chemotherapy have to be defined.Thalidomide's mechanism of action is still unclear. There are, however, several hypotheses regarding its mode of action. Recently, several analogues of thalidomide-the so-called ImiDs, have been developed. Preclinical data indicate that they might be more effective and less toxic than thalidomide. Trials evaluating the ImiDs in the clinical setting are still ongoing.In this paper, we will review the available clinical data regarding efficacy and toxicity of thalidomide, discuss its possible mechanism of action and point to future directions of research and clinical development of the ImiDs.     

New treatment of multiple myeloma

PURPOSE: After decades of minimal progress, two new classes of drugs with novels mechanisms of action: immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib) have shown great activity for the treatment of multiple myeloma. CURRENT KNOWLEDGE AND KEY POINTS: Thalidomide acts by a variety of mechanisms; its efficacy is well known in disease relapse especially associated with dexamethasone. Recent results prove that combination of thalidomide with melphalan and prednisone should be considered as the first line standard of care in elderly patient. The main side effects are peripheral neuropathy and deep-vein thrombosis. Bortezomib is the first proteasome inhibitor. It is approved for the treatment in first disease relapse. The combination with glucocorticoids is synergistic. This combination in induction treatment before autologous stem cell transplantation is promising, as well as the combination with melphalan and prednisone in elderly patient. The main toxicities are fatigue and peripheral neuropathy. Lenalidomide is a structural analogue of thalidomide. Its efficacy in combination with dexamethasone has been proved in relapsing patients. The main toxicity is hematologic. Utilisation as first line treatment is also promising. FUTURE PROSPECTS AND PROJECTS: These three drugs have toxicities predictable and manageable and can be used successively or in combination for greater effectiveness. They have an impact on the multiple myeloma treatment strategies and on the disease course itself.     

多发性骨髓瘤的个体化治疗

多发性骨髓瘤（multiple myeloma,MM）是一种在中、老年人中发病率较高,严重危害人类健康的浆细胞恶性增生性血液肿瘤.虽然放疗、化疗及干细胞移植在MM患者中可取得一定疗效,但MM目前仍是一种无法根治的疾病,且长期完全缓解者极少。新近研究已发现了一些具有独特作用机制的药物（如沙利度胺、雷纳利度胺、硼替佐米等）,同时随着近年来对骨髓瘤细胞生物学了解的深入,