Prognostic Value of Bone Marrow Angiogenesis in Multiple Myeloma

• Published in: Clinical cancer research 2000-08, Vol.6 (8), p.3111-3116
• Main Authors: RAJKUMAR, S. V, LEONG, T, GREIPP, P. R, ROCHE, P. C, FONSECA, R, DISPENZIERI, A, LACY, M. Q, LUST, J. A, WITZIG, T. E, KYLE, R. A, GERTZ, M. A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Bone Marrow - blood supply; Bone Marrow - pathology; Clinical Trials as Topic; Female; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Multiple Myeloma - blood supply; Multiple Myeloma - pathology; Multiple Myeloma - therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Plasma Cells - metabolism; Plasma Cells - pathology; Prognosis; Survival Analysis; Treatment Outcome; von Willebrand Factor - metabolism
• ISSN: 1078-0432; 1557-3265

We studied the prognostic value of angiogenesis grading and microvessel density estimation in newly diagnosed multiple myeloma. Seventy-five patients with newly diagnosed myeloma, treated on Eastern Cooperative Oncology Protocol E9486 and Intergroup study 0141 (S9321) at the Mayo Clinic, were studied. Bone marrow microvessels were examined using immunohistochemical staining for von Willebrand factor. Determination of microvessel density and angiogenesis grading was done in a blinded manner. There was a strong correlation between microvessel density and the plasma cell labeling index, rho 0.42, P < 0.001. Angiogenesis grade was also significantly associated with the plasma cell labeling index. Fifteen % of patients with low-grade angiogenesis had a high labeling index (>1%). In contrast, 47% of patients with intermediate or high-grade angiogenesis had high labeling indices ( P = 0.02). Overall survival was significantly different among those with high-, intermediate-, and low-grade angiogenesis, with median times of 2, 4, and 4.4 years, respectively ( P = 0.02). Similarly, patients with microvessel density >50/×400 field had poorer survival compared with those with 50 or fewer microvessels/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 predictor of poor survival in newly diagnosed myeloma. Angiogenesis is correlated with the plasma cell labeling index but not the bone marrow plasma cell percentage. A simple visual grading of angiogenesis is an efficient alternative to microvessel density estimation.