Kumar S, Witzig T E, Dispenzieri A, Lacy M Q, Wellik L E, Fonseca R, Lust J A, Gertz M A, Kyle R A, Greipp P R, Rajkumar S V
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Leukemia. 2004 Mar;18(3):624-7. doi: 10.1038/sj.leu.2403285.
Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an important prognostic factor for survival. Previous studies have shown that BM angiogenesis does not change following chemotherapy or stem cell transplant. Given its potential antiangiogenic effect, we evaluated if thalidomide therapy would affect the BM microvessel density (MVD). We studied BM angiogenesis in 81 patients with various disease stages treated with thalidomide with or without dexamethasone. MVD was determined as previously described. MVD was compared between pretreatment marrows and those obtained 4-6 months following therapy. The median (range) MVD pretherapy was 28 (2-116) and post-therapy was 15 (3-97). A partial or complete response was seen in 58% of patients, stable disease in 41% and progressive disease in one patient. MVD decreased significantly in responders (median decrease of 12, P<0.001). In contrast, no significant change in MVD was seen in those failing to respond to thalidomide. Unlike the lack of resolution of angiogenesis reported with other therapies, we demonstrate for the first time a significant decrease in microvessels with thalidomide therapy. Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma.
多发性骨髓瘤患者的骨髓血管生成增加，且是生存的重要预后因素。既往研究表明，化疗或干细胞移植后骨髓血管生成无变化。鉴于沙利度胺具有潜在的抗血管生成作用，我们评估了沙利度胺治疗是否会影响骨髓微血管密度（MVD）。我们研究了81例接受沙利度胺治疗（联合或不联合地塞米松）的不同疾病分期患者的骨髓血管生成情况。MVD的测定方法如前所述。比较治疗前骨髓与治疗4 - 6个月后获得的骨髓的MVD。治疗前MVD的中位数（范围）为28（2 - 116），治疗后为15（3 - 97）。58%的患者出现部分或完全缓解，41%病情稳定，1例病情进展。缓解者的MVD显著降低（中位数降低12，P<0.001）。相比之下，对沙利度胺无反应者的MVD无显著变化。与其他治疗方法所报道的血管生成未消退不同，我们首次证明沙利度胺治疗可使微血管显著减少。尽管尚无定论，但这一结果进一步支持了血管生成是骨髓瘤相关治疗靶点的假说。
