title: Treatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and bone marrow thrombospondin concentration.
abstract: Multiple myeloma (MM) is associated with increased rate of bone marrow angiogenesis. Increased concentration of hepatocyte growth factor (HGF) is associated with poor prognosis in patients treated with conventional chemotherapy or thalidomide. We have shown previously that decreased level of thrombospondin, an angiogenesis inhibitor, correlates with poor response to high-dose chemotherapy. The aim of our current study was to evaluate association between therapeutic response to bortezomib and thrombospondin and HGF levels. Peripheral blood plasma concentration of HGF and bone marrow plasma concentration of thrombospondin were measured in patients with MM prior to the initiation of bortezomib therapy. Overall, 58 patients were enrolled, 44/58 (76%) of them with relapsed disease. Treatment outcomes were analyzed for possible associations with pretreatment HGF and thrombospondin levels. Patients who achieved complete response had significantly higher pretreatment HGF levels and lower pretreatment thrombospondin levels than others. More than 70% of patients with low pretreatment HGF and high pretreatment thrombospondin concentrations achieved very good partial response or complete response, in contrast to only 20% of patients with high HGF and low thrombospondin levels. High pretreatment thrombospondin and low pretreatment HGF concentrations are associated with therapeutic response to bortezomib in patients with MM.
authors.affiliation: Department of Internal Medicine-Hematooncology, University Hospital Brno, Masaryk University, Brno, Czech Republic. lpour@fnbrno.cz
authors.forename: Pour
authors.initials: P
authors.lastname: Ludek
authors.forename: Svachova
authors.initials: S
authors.lastname: Hana
authors.forename: Adam
authors.initials: A
authors.lastname: Zdenek
authors.forename: Almasi
authors.initials: A
authors.lastname: Martina
authors.forename: Kralova
authors.initials: K
authors.lastname: Dana
authors.forename: Buchler
authors.initials: B
authors.lastname: Tomas
authors.forename: Kovarova
authors.initials: K
authors.lastname: Lucie
authors.forename: Krejci
authors.initials: K
authors.lastname: Marta
authors.forename: Michalek
authors.initials: M
authors.lastname: Jaroslav
authors.forename: Penka
authors.initials: P
authors.lastname: Miroslav
authors.forename: Vorlicek
authors.initials: V
authors.lastname: Jiri
authors.forename: Hajek
authors.initials: H
authors.lastname: Roman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001853:Bone Marrow / Q000378:metabolism*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy; D011719:Pyrazines / Q000008:administration & dosage*; D012008:Recurrence; D019699:Thrombospondins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D019699:Thrombospondins; D017228:Hepatocyte Growth Factor; D000069286:Bortezomib