title: High serum vascular endothelial growth factor level is an adverse prognostic factor for high-risk diffuse large B-cell lymphoma patients treated with dose-dense chemoimmunotherapy.
abstract: OBJECTIVE
  To determine whether serum vascular endothelial growth factor (s-VEGF) levels and VEGF gene expression in tumor tissue predict survival of diffuse large B-cell lymphoma (DLBCL) patients treated with chemoimmunotherapy.
  
  
  METHODS
  VEGF levels were measured in serum samples from 102 patients <65 yrs with high-risk DLBCL using a quantitative sandwich enzyme immunoassay technique. Exon array data set of tumor tissues from 32 patients was concurrently used to determine VEGF-A exon and gene expression. All patients were treated in a Nordic phase II study with six dose-dense chemoimmunotherapy courses followed by systemic central nervous system prophylaxis.
  
  
  RESULTS
  After a median follow-up time of 40 months, 3-yr progression-free survival (PFS) was inferior in patients with high s-VEGF levels compared to those with low levels (59% vs. 83%, P = 0.005). The relative risk of progression or relapse was 3.1-fold (95% confidence interval 1.34-6.91, P = 0.008). The predictive capacity of s-VEGF levels on PFS was most pronounced in the DLBCLs of non-germinal center subtype. In contrast to serum data, VEGF mRNA expression in the lymphoma tissue did not predict outcome, and no correlation was found between s-VEGF levels and lymphoma VEGF expression.
  
  
  CONCLUSIONS
  Pretreatment s-VEGF level is a predictor of PFS after chemoimmunotherapy and may help to further stratify high-risk DLBCL patients into low- and high-risk groups.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Riihijärvi
authors.forename: Heidi
authors.initials: H
authors.lastname: Nurmi
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Oystein
authors.initials: O
authors.lastname: Fluge
authors.forename: Lars Møller
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Karin
authors.initials: K
authors.lastname: Rydström
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Sirpa
authors.initials: S
authors.lastname: Leppä
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A