摘要
目的探讨低剂量环磷酰胺联合泼尼松节律性化疗对多发性骨髓瘤（MM）患者骨髓组织微血管密度（MVD）和外周血中血管内皮生长因子（VEGF）、血小板衍生生长因子BB（PDGF—BB）表达的影响。方法54例难治或复发性MM患者给予低剂量环磷酰胺（50mg／d）联合泼尼松（15mg／d）（cP方案）持续口服。在治疗前和治疗后2、4、6个月分别取患者骨髓组织及外周血，应用免疫组织化学法分析患者的骨髓组织MVD，ELISA法检测外周血中VEGF和PDGF—BB表达水平。结果在可评估的37例患者中，30例患者有效，有效率为81．08％。其余17例患者随访未达6个月或未能获得血清检测标本或失访。低剂量环磷酰胺联合泼尼松节律性化疗2、4、6个月后，有效组30例患者MVD计数分别为33．1±4．8／高倍视野（HP）、24．8±3．7／HP、19．7±2．1／HP；外周血VEGF水平分别为（394±57）、（268±32）、（217±20）ng／L；PDGF—BB水平分别为（304±31）、（274±31）、（196±22）ng／L。与治疗前[MVD为48．5±5．9／HP，VEGF为（517±60）ng／L，PDGF—BB为（484±60）ng／L]相比，患者骨髓MVD和外周血VEGF、PDGF—BB表达水平显著降低（P值均〈0．01）。而无效组7例患者在化疗后2个月MVD为32．54-4．7／HP，外周血VEGF水平为（512±39）ng／L，PDGF-BB水平为（452±39）ng／L，与治疗前[MVD为33．2±5．6／HP，VEGF为（498±55）ng／L，PDGF—BB为（488±44）ng／L]相比差异无统计学意义（P值均〉0．05）。结论低剂量环磷酰胺联合泼尼松节律性化疗可明显降低MM患者骨髓组织MVD和血清VEGF、PDGF—BB表达水平。其在MM中的作用机制可能与抑制新生血管的生成有关。
Objective To investigate effects of low-dose cyclophosphamide and prednisone （CP） metronomic chemotherapy on mierovessel density of bone marrow, serum vascular endothelial growth factor （VEGF） and platelet derived growth factor BB （PDGF-BB）in muhiple myeloma （MM） patients. Methods 54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral eyclo- phosphamide （CTX, 50 mg/d） and prednisone （Pred, 15 mg/d）. Bone marrow and peripheral blood of each patient were collected before and 2,4,6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Mierovessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients. Results 2,4,6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2. 1/HP respectively; the expressions of VEGF were （394 ±57） ng/L, （268 ± 32） ng/L and （217 ± 20） ng/L respectively; the expressions of PDGF-BB were （304 ± 31 ） ng/L, （274 ± 31 ） ng/L and （196 ± 22） ng/L respectively. After CP metronom- ic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment [ MVD 48.5 ±5.9/HP, VEGF （517 ±60） ng/L, PDGF-BB （484 ± 60） ng/L] in the re- sponders （P 〈 0.01 ）. While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ±39 ng/L and （452 ± 39） ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment [ MVD 33.2 ± 5.6/HP, VEGF （498 ± 55 ） ng/L, PDGF-BB （488 ± 44 ） ng/L ] （P 〉 0.05 ）. Conclusions Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2012年第6期457-460,共4页
Chinese Journal of Hematology
关键词
环磷酰胺
泼尼松
多发性骨髓瘤
血管内皮生长因子
血小板衍生生长因子
微血管密度
节律性化疗
Cyclophosphamide
Prednisone
Multiple myeloma
Vascular endothelial growth factor
Platelet derived growth factor
Microvessel density
Metronomic chemotherapy
