1700632080 [20] Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase Ⅱ study. Lancet, 2008, 371(9624):1579-1586.

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1700632082 [21] Kotloff RM, Ahya VN, Crawford SW. Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation. Am J Respir Crit Care Med, 2004, 70(1):22-48.

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1700632084 [22] 徐志松，周建英，黄河．异基因骨髓移植后不同时期感染并发症的临床研究．中华血液学杂志，2004，25(8):496-498.

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1700632086 [23] Kenneth V, Rolston I. The infectious diseases society of america 2002 Guidelines for the use of antimicrobial agents in patients with cancer and neutropenia: salient features and comments. Clin Infect Dis, 2004, 39(Suppl 1):44-48.

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1700632088 [24] Ortega M, Rovira M, Almela M, et al. Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol, 2005, 84(1):40-46.

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1700632090 [25] Karthaus M, Cornely OA. Recent developments in the management of invasive fungal infections in patients with hematological malignancies. Ann Hematol, 2005, 84(4):207-216.

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1700632092 [26] 中华内科杂志编辑委员会．血液病／恶性肿瘤患者侵袭性真菌感染的诊断标准与治疗原则（修订版）．中华内科杂志，2007，46(7):607-610.

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1700632094 [27] Gentile G, Picardi A, Capobianchi A, et al. A prospective study comparing quantitative Cytomegalovirus（CMV）polymerase chain reaction in plasma and pp65 antigenemia assay in monitoring patients after allogeneic stem cell transplantation. BMC Infect Dis, 2006, 6:167.

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1700632096 [28] Stewart S. Pulmonary infections in transplantation pathology. Arch Pathol Lab Med, 2007, 131(8):1219-1231.

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1700632098 [29] Porter D, Levine JE. Graft-versus-host disease and graft-versus-leukemia after donor leukocyte infusion. Semin Hematol, 2006, 43(1):53-61.

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1700632100 [30] Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol, 2007, 25(31):4938-4945.

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1700632102 [31] Fowler DH. Shared biology of GVHD and GVT effects: potential methods of separation. Crit Rev Oncol Hematol, 2006, 57(3):225-244.

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1700632104 [32] Rezvani AR, Storb RF. Separation of graft-vs.-tumor effects from graft-vs.-host disease in allogeneic hematopoietic cell transplantation. J Autoimmun, 2008, 30(3):172-179.

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1700632106 （黄　河）

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1700632108

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1700632110

1700632111 内科学新进展 [:1700627011]

1700632112 内科学新进展 第五节　多发性骨髓瘤研究现状

1700632113

1700632114 摘　要　多发性骨髓瘤（MM）是恶性浆细胞克隆性疾病，占血液系统恶性肿瘤的10％以上，近年来发病率有逐渐增高的趋势，其特征为骨髓恶性浆细胞克隆增生、血清免疫球蛋白升高、溶骨性骨骼破坏。近年来MM的诊断和病情评估已取得了长足进步：新的简便的分期系统（ISS）广泛应用于临床并正取代Durie-Salmon分期；国际统一的疗效标准出现；血清游离轻链检测的进展；细胞遗传学异常对于患者诊断、分型和预后判断的意义正在得到广泛认可。基因组学和蛋白组学的研究给MM的研究带来大量新的信息，许多靶分子得到鉴定并用于诊断和研发新的MM治疗药物。免疫调节药（thalidomide, lenolidomide）和蛋白酶体抑制剂（bortezomib）给MM的治疗带来革命性的变化；临床研究证实干细胞移植和移植后维持治疗的重要性。由于针对骨髓瘤细胞及其生长微环境的靶向新药不断涌现，这些进展使得MM的治疗选择越来越具有多样性，总体生存期越来越长，生活质量越来越高。本节综述MM研究现状，主要概述MM的发病机制、分型、分期、临床表现、诊断标准等，并讨论MM干细胞移植和药物治疗，包括一些新药、诊断和预后的进展。

1700632115

1700632116 Abstract　Multiple myeloma（MM）is clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. The incidence has gradually increased in recent years. MM is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic lesions. Significant advances include a simplified staging system, which has replaced the Durie-Salmon staging system; an updated uniform international response criteria; the development of a sensitive new serum test to detect free light chain production, the recognition of specific adverse cytogenetic abnormalities. And the evolution of genomics, which will identify specific and targeted therapies for individual MM patients. For the first time in decades, major therapeutic advances have been implemented in the treatment of MM patients. These include 2 new classes of agent: immunomodulatory drugs and proteosome inhibitors. In addition, clinical trials have solidified the role of hematopoietic stem cell transplant and established the benefits of post-transplant maintenance therapy. A number of new agents are in development that specifically target the myeloma cells and the bone marrow microenvironment. These advances have resulted in expanded treatment options, prolonged disease control and survival, and improved quality of life for patients with MM. In this chapter, we present a focused review of the disease, the mechanism, typing and staging, clinical manifestation, diagnosis criteria, the evolution of drug therapy and stem-cell transplantation for the treatment of MM, as well as the development of new agents and so on is discussed. We also provide an update on current concepts of diagnosis and prognosis.

1700632117

1700632118 多发性骨髓瘤（multiple myeloma, MM）又称浆细胞骨髓瘤，是发生在浆细胞的恶性克隆增殖性疾病。骨髓内单克隆浆细胞恶性增生并分泌大量单克隆免疫球蛋白，血清出现单克隆免疫球蛋白，正常多克隆浆细胞增生和多克隆免疫球蛋白分泌受到抑制，尿内出现本周氏蛋白，引起广泛溶骨性破坏、反复感染、贫血、高钙血症、高黏滞综合征、肾功能不全等临床表现。

1700632119

1700632120 一、病因学

1700632121

1700632122 MM的病因目前尚未完全明确。电离辐射、慢性抗原刺激、遗传因素、病毒感染等可能与MM发病有关。研究发现放射线职业人群的发病率显著高于正常人群，发病率高低与接受的放射线剂量成正相关，提示电离辐射可诱发此病。少数文献报告某些化学物质如石棉、砷、杀虫剂、石油、塑料、橡胶类长期接触可诱发此病。长期慢性抗原刺激者较易发生MM。

1700632123

1700632124 二、发病机制

1700632125

1700632126 浆细胞由B淋巴细胞发育、分化而来，是一个多步骤且涉及多个解剖部位的过程。目前认为多发性骨髓瘤细胞虽然主要表现B细胞—浆细胞特点，但起源却是较前B细胞更早的造血前体细胞的恶变。至于造血前体细胞发生恶变的机制，目前尚未完全阐明。近年来也有学者认为MM细胞来源自分化晚期的B细胞。

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1700632128 （一）分子遗传学改变

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