Prognostic value of bone marrow angiogenesis in multiple myeloma

We studied the prognostic value of angiogenesis grading and microvessel den sity estimation in newly diagnosed multiple myeloma, Seventy-five patients with newly diagnosed myeloma, treated on Eastern Cooperative Oncology Proto col E9486 and Intergroup study 0141 (S9321) at the Mayo Clinic, were studie d. Bone marrow microvessels were examined using immunohistochemical stainin g for von Willebrand factor. Determination of microvessel density and angio genesis grading,vas done in a blinded manner. There was a strong correlatio n between microvessel density and the plasma cell labeling index, rho 0.42, P < 0.001. Angiogenesis grade,vas also significantly associated with the p lasma cell labeling index. Fifteen % of patients,vith low-grade angiogenesi s had a high labeling index (>1%), In contrast, 47% of patients with interm ediate or high-grade angiogenesis had high labeling indices (P = 0.02), Ove rall survival was significantly different among those with high-, intermedi ate-, and low-grade angiogenesis, with median times of 2, 4, and 4.4 years, respectively (P = 0.02), Similarly, patients with microvessel density >50/ x400 field had poorer survival compared with those with 50 or fewer microve ssels/field, median survival 2.6 versus 5.1 years, respectively (P = 0.004) , There was a strong association between angiogenesis grade and microvessel density (P < 0.001). We conclude that bone marrow angiogenesis is a predic tor of poor survival in newly diagnosed myeloma, Angiogenesis is correlated with the plasma cell labeling index but not the bone marrow plasma cell pe rcentage. A simple visual grading of angiogenesis is an efficient alternati ve to microvessel density estimation.