多发性骨髓瘤细胞遗传学变化及其蛋白酶体抑制剂的疗效观察

目的分析多发性骨髓瘤(MM)的细胞遗传学变化及其与蛋白酶体抑制剂治疗的关系。方法对2005年1月至2006年7月北京大学人民医院29例初诊的MM患者行染色体核型检查,采用骨髓细胞24h短期培养,用常规方法制备染色体,G显带进行核型分析。22例MM患者采用传统化疗即长春新碱联合阿霉素和地塞米松(VAD)方案或马法兰与泼尼松(MP)方案;7例患者应用蛋白酶体抑制剂(硼替佐米)为主的化疗方案。比较两组患者的有效率及缓解率。结果29例MM患者中异常核型检出率为37.9%,其中有复杂和高度复杂畸变的占81.8%。采用VAD或MP方案化疗的核型正常组的有效率为81.2%,核型异常组有效率为0,差异有显著性意义(P<0.05)。应用硼替佐米为主的化疗方案中核型异常组5例均有效,核型正常组2例均有效。核型异常组硼替佐米有效率与传统化疗组相比,差异有显著性意义(P<0.05)。结论染色体核型异常的患者,应首选蛋白酶体抑制剂硼替佐米等进行治疗。

Proteasome inhibitors(bortezomib) reverse the adverse effect of abnormal chromosome on multiple myeloma

Objective To study cytogenetic features of multiple myeloma(MM)cells and the relationship between chromosomal karyotypes and subtype,stage,prognostic parameters and treatment of MM.Methods Karyotyping in patients with MM by 24h short-term bone marrow cell culture and G-banding stain were done.Twenty-two patients were treated with conventional chemotherapy(VAD or MP)and 7 patients with Bortezomib(velcade)chemotherapy.Results There was 37.9% of aberrations in patients with multiple myeloma of 29 cases,and the complex and high complex aberrations were 81.8%.Twenty-two patients with VAD or MP chemotherapy;response rate was 81.2% in normal karyotype group;no response was received in the abnormal karyotypes group(P<0.05).There were 7 patients with bortezomib chemotherapy,5 were in abnormal karyotypes group,2 cases of 7 were in normal karyotypes group,both of response rates in two groups being 100%.The response rates with bortezomib chemotherapy compared with conventional chemotherapy in patients with multiple myeloma were superior(P<0.05).Conclusion Myeloma patients with chromosomal abnormalities receive minimal benefit from conventional therapy and are candidates for novel therapeutic approaches such as proteasome inhibitors(bortezomib).