title: Prognostic value of bone marrow angiogenesis in multiple myeloma.
abstract: 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/x400 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.
authors.affiliation: Division of Hematology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. rajks@mayo.edu
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: T
authors.initials: T
authors.lastname: Leong
authors.forename: P C
authors.initials: PC
authors.lastname: Roche
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: J A
authors.initials: JA
authors.lastname: Lust
authors.forename: T E
authors.initials: TE
authors.lastname: Witzig
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
mesh_terms: D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009101:Multiple Myeloma / Q000098:blood supply* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor