Bone marrow angiogenesis and its clinical correlates in myelofibrosis with myeloid metaplasia

Abstract

BACKGROUND AND OBJECTIVES: Previous retrospective studies have indicated markedly increased bone marrow angiogenesis (BMA) in myelofibrosis with myeloid metaplasia (MMM). This issue is further examined in the current prospective study and clinico-pathological correlates sought. DESIGN AND METHODS: This was a prospective single institutional study of 66 patients with bone marrow biopsy-proven MMM who were consecutively accrued. Bone marrow angiogenesis was evaluated by assessing microvessel density through immunohistochemical staining for the CD34 antigen. Laboratory and clinical information was collected concurrently. RESULTS: The 66 patients (median age 62 years, 46 males) included 36 with fibrotic phase agnogenic myeloid metaplasia (AMM), 6 with cellular phase AMM, 4 with hypocellular variant AMM, 10 with post-polycythemic myeloid metaplasia, and 10 with post-thrombocythemic myeloid metaplasia. Overall, increased BMA was documented in 61 patients (92%). All of the aforementioned sub-categories of MMM were similarly affected in terms of either grade 3 or 4 BMA but differed in the prevalence of grade 4 BMA (25%, 0%, 0%, 10%, and 10%, respectively). In a univariate analysis the only histological feature that significantly correlated with BMA was the degree of megakaryocyte clustering. Among clinical features, increased BMA was significantly associated with younger age of the patient, lower hemoglobin level, intact spleen, and absence of active therapy. On multivariate analysis, only the latter two retained their significance. INTERPRETATION AND CONCLUSIONS: The current prospective study confirms the consistent association of BMA with MMM and suggests that the process starts early, is progressive, and might be dampened by both splenectomy and drug therapy. The study also suggests either a megakaryocyte origin or a megakaryocyte effect for the putative angiogenic cytokine.