title: Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines,angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome.
abstract: OBJECTIVE
  In vitro studies suggest that thalidomide has an immunoregulatory role and alters the marrow microenvironment. We assessed laboratory and clinical parameters in patients with myeloma treated with thalidomide as potential prognostic markers and looked for changes with therapy.
  
  
  METHODS
  Seventy-five patients with relapsed/refractory myeloma received thalidomide in a phase II trial. Serial samples of platelet-poor plasma and bone marrow were tested for angiogenic cytokines including vascular endothelial growth factor (VEGF), marrow microvessel-density (MVD), mast cells and CD57+ cell expression. The effects of these parameters on response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed.
  
  
  RESULTS
  Elevated baseline VEGF predicted for a superior RR (p=0.018) and PFS. Elevated CD57+ cells also predicted superior PFS (p=0.012). MVD did not predict for RR, PFS or OS, but MVD and VEGF fell significantly in responders. Multivariate analysis identified that inferior OS was associated with age >65 years (p=0.017), raised lactate dehydrogenase (p=0.001), raised hepatocyte growth factor levels (p=0.012) and low pre-treatment CD57+ cells (p<0.001).
  
  
  CONCLUSIONS
  Our findings support the suggestion that thalidomide has anti-angiogenic and immunomodulatory effects in myeloma. The preferred method for assessing angiogenesis is plasma VEGF levels and the assessment of CD57+ cells for patients with myeloma receiving novel immunomodulatory drugs should be further investigated.
authors.affiliation: Division of Haematology and Medical Oncology, Department of Haematology and Medical Oncology, Peter MacCallum Cancer Center, St Andrew's Place, East Melbourne, VIC, Australia. Linda.Mileshkin@petermac.org
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
authors.forename: Dirk
authors.initials: D
authors.lastname: Honemann
authors.forename: Peter
authors.initials: P
authors.lastname: Gambell
authors.forename: Melanie
authors.initials: M
authors.lastname: Trivett
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Mark
authors.initials: M
authors.lastname: Smyth
authors.forename: Victoria
authors.initials: V
authors.lastname: Beshay
authors.forename: David
authors.initials: D
authors.lastname: Ritchie
authors.forename: Paul
authors.initials: P
authors.lastname: Simmons
authors.forename: Alvin D
authors.initials: AD
authors.lastname: Milner
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000473:pathology*; D018959:CD57 Antigens / Q000032:analysis*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000473:pathology*; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018959:CD57 Antigens; D016207:Cytokines; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D013792:Thalidomide