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


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).


CONCLUSIONS
There is no relationship between MVD estimation and baseline serum levels of angiogenic cytokines, neither between each of them and response to therapy.
Cibeira
M Teresa
MT
Hematology Department, Institute of Hematology and Oncology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Villarroel 170, Barcelona 08036, Spain.
Rozman
María
M
Segarra
Marta
M
Lozano
Esther
E
Rosiñol
Laura
L
Cid
Maria C
MC
Filella
Xavier
X
Bladé
Joan
J
D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002196:Capillaries / Q000473:pathology; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D001897:Boronic Acids; D016207:Cytokines; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide