Bone marrow angiogenesis and angiogenic factors in multiple myeloma treated with novel agents

Cytokine. 2008 Mar;41(3):244-53. doi: 10.1016/j.cyto.2007.11.017. Epub 2008 Jan 4.

Abstract

Introduction: An increased bone marrow (BM) angiogenesis is associated with poor outcome in multiple myeloma (MM).

Objective: Angiogenesis study in MM treated with novel antimyeloma agents: thalidomide, lenalidomide, bortezomib, and with dexamethasone.

Patients and methods: Forty-four patients with MM (14 newly diagnosed, 30 refractory/relapsed) were treated with novel agents at our institution. A BM biopsy was obtained before the initiation of therapy in 19. Angiogenesis was assessed by microvessel density (MVD) estimation in BM biopsies stained with the monoclonal anti-CD34 antibody, and by serum levels of angiogenic factors (VEGF, bFGF, and HGF) and cytokines (IL-6 and TNF-alpha).

Results: A positive correlation was found between BM plasma cell involvement and MVD estimation (p=0.01). However, MVD was not significantly correlated with either disease phase (p=0.065) or response to therapy (p=0.79). Neither baseline serum levels of angiogenic cytokines correlated to response to treatment. No significant correlation was found between BM MVD and serum levels of angiogenic cytokines. Serum levels of angiogenic cytokines before and after therapy showed a significant increase of bFGF (p=0.008).

Conclusion: There is no relationship between MVD estimation and baseline serum levels of angiogenic cytokines, neither between each of them and response to therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenic Proteins / blood*
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / blood supply*
  • Bone Marrow / pathology
  • Boronic Acids / therapeutic use
  • Bortezomib
  • Capillaries / pathology
  • Cytokines / blood
  • Dexamethasone / therapeutic use
  • Female
  • Humans
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Neovascularization, Pathologic / diagnosis*
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Pyrazines / therapeutic use
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use

Substances

  • Angiogenic Proteins
  • Antineoplastic Agents
  • Boronic Acids
  • Cytokines
  • Pyrazines
  • Thalidomide
  • Bortezomib
  • Dexamethasone
  • Lenalidomide