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多发性骨髓瘤的治疗策略:现状

Therapy strategies for multiple myeloma: current status.

作者信息

Gisslinger Heinz, Kees Mathias

机构信息

Division of Haematology and Blood Coagulation, Department of Internal Medicine I, University of Vienna, Vienna, Austria.

出版信息

Wien Klin Wochenschr. 2003 Aug 14;115(13-14):451-61. doi: 10.1007/BF03041028.

Abstract

Multiple myeloma (MM) is characterized by infiltration of bone marrow with a clone of neoplastic plasma cells. Impaired hematopoiesis and reduced production of functional immunoglobulins, as well as the induction of pathognomonic osteolytic lesions primarily contribute to the morbidity of patients with MM. Conventional chemotherapy is the treatment of choice for older patients, whereas those under 60 years benefit significantly from high-dose therapy followed by stem-cell rescue. The use of tandem transplantation, developed to further escalate the conditioning dose, has achieved additional improvement in survival. Interferon-alpha and glucocorticoids are effective as maintenance measures in MM but remain controversial because of their associated high costs and considerable toxicity. The resurrection of an old drug, thalidomide, for the therapy of MM and the development of potent immunomodulatory derivatives are highly promising new treatments that target MM cell-host interactions and the bone-marrow microenvironment, as well as the myeloma cell itself. The importance of the use of bisphosphonates for the prevention or amelioration of skeletal complications and hypercalcemia is well established. New generations of bisphosphonates show potent antitumor activity, again emphasising the importance of targeting the microenvironment of the plasma-cell clone.

摘要

多发性骨髓瘤(MM)的特征是骨髓被一群肿瘤性浆细胞浸润。造血功能受损、功能性免疫球蛋白产生减少,以及典型溶骨性病变的形成,这些主要导致了MM患者的发病。传统化疗是老年患者的首选治疗方法,而60岁以下的患者从大剂量治疗后进行干细胞救援中获益显著。为进一步提高预处理剂量而开发的串联移植,已使生存率得到了额外的改善。α干扰素和糖皮质激素作为MM的维持治疗措施有效,但因其相关的高成本和相当大的毒性而仍存在争议。一种旧药沙利度胺用于MM治疗的复兴以及强效免疫调节衍生物的开发,是极具前景的新疗法,它们靶向MM细胞与宿主的相互作用、骨髓微环境以及骨髓瘤细胞本身。使用双膦酸盐预防或改善骨骼并发症和高钙血症的重要性已得到充分证实。新一代双膦酸盐显示出强大的抗肿瘤活性,再次强调了靶向浆细胞克隆微环境的重要性。

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