Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia

Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis, Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, i ncluding multiple myeloma. The extent and prognostic significance of bone m arrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplas ia (MMM) was investigated. A control group of 44 patients without bone marr ow disease, 15 patients with polycythemia vera, and 17 patients with essent ial thrombocythemia was also studied. Bone marrow microvessel density was a ssessed by a semiquantitative method, visual microvessel grading, and 2 sep arate quantitative methods, visual count and computerized image analysis. A ngiogenesis estimation by all 3 methods was highly comparable, On visual mi crovessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia,and 0% of normal cont rols. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angio genesis correlated with hypercellularity and megakaryocyte clumping. in con trast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibr osis, These preliminary findings suggest that neo-angiogenesis is an integr al component of the bone marrow stromal reaction in MMM and may provide use ful prognostic information and a rationale for the therapeutic investigatio n of anti-angiogenic agents. (C) 2000 by The American Society of Hematology .