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[生物疗法在多发性骨髓瘤中的作用]

[The role of biotherapy in multiple myeloma].

作者信息

Petrucci M T, Tafuri A, Mandelli F

机构信息

Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma.

出版信息

Recenti Prog Med. 2000 Oct;91(10):488-93.

Abstract

Despite considerable progress in recent years in the understanding of the biology of multiple myeloma (MM), this disease remains incurable, although many new therapeutic approaches are under evaluation. The rapid development of recombinant technologies has permitted the production of large amounts of cytokines and growth factors, favoring the use of biotherapies also in this disease. Among these products, the interferons have been the most extensively used in clinical trials, giving the most promising results especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies, or to high dose chemotherapies followed by bone marrow (BM) or peripheral blood stem cell (PBSC) transplantation. However, more recently, a large number of cytokines and growth factors have been introduced in the clinical practice. Data of the use of erythropoietin have consistently demonstrated the role of this growth factor in ameliorating the grade of anemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Using hematopoietic growth factor in the mobilization of PBSC, the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of chemotherapy could be reduced. Despite the large amount of experimental data indicating a role for interleukins, as IL-2 and IL-6, in controlling tumor growth, there are only few clinical studies dealing with their use in MM. Results show that they arrest tumor progression rather than aid tumor regression, for this reason it appears that IL-2 and anti IL-6 antibodies should be investigated as maintenance therapy, in MM patients responding to chemotherapy. In the future it will be necessary to clarify for MM patients the role of other cytokines such as IL-1 beta and TNF alpha. A possible strategy to improve the clinical outcome of MM patients is to prevent the regrowth of residual tumor cells by establishing adoptive immunity at the stages of minimal residual disease previous obtained using chemotherapy. To this end a possible strategy is to induce an immune response against residual tumor cells by passive (using monoclonal antibodies) or active (using the idiotype expressed by malignant cells) immunotherapy.

摘要

尽管近年来在多发性骨髓瘤(MM)生物学理解方面取得了显著进展,但这种疾病仍然无法治愈,不过许多新的治疗方法正在评估中。重组技术的迅速发展使得能够大量生产细胞因子和生长因子,这也有利于在该疾病中使用生物疗法。在这些产品中,干扰素在临床试验中使用最为广泛,尤其在微小残留病的情况下,作为对传统疗法或高剂量化疗后进行骨髓(BM)或外周血干细胞(PBSC)移植后的维持治疗,给出了最有希望的结果。然而,最近大量的细胞因子和生长因子已被引入临床实践。使用促红细胞生成素的数据一直表明,这种生长因子在改善贫血程度以及疾病并发严重或中度贫血的MM患者生活质量方面的作用。在PBSC动员中使用造血生长因子,外周血中祖细胞数量增加,化疗的血液学毒性可以降低。尽管大量实验数据表明白细胞介素如IL - 2和IL - 6在控制肿瘤生长中起作用,但仅有少数临床研究涉及它们在MM中的使用。结果表明它们阻止肿瘤进展而非促进肿瘤消退,因此对于对化疗有反应的MM患者,似乎应研究将IL - 2和抗IL - 6抗体作为维持治疗。未来有必要为MM患者阐明其他细胞因子如IL - 1β和TNFα的作用。改善MM患者临床结局的一种可能策略是,在先前使用化疗获得的微小残留病阶段,通过建立过继性免疫来防止残留肿瘤细胞的再生长。为此,一种可能的策略是通过被动(使用单克隆抗体)或主动(使用恶性细胞表达的独特型)免疫疗法诱导针对残留肿瘤细胞的免疫反应。

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