title: Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study.
abstract: OBJECTIVE
  POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome.
  
  
  METHODS
  This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival.
  
  
  RESULTS
  Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months.
  
  
  CONCLUSIONS
  Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Misawa
authors.affiliation: Clinical Research Center, Chiba University Hospital, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Clinical Research Center, Chiba University Hospital, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Clinical Research Center, Chiba University Hospital, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hanaoka
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sawai
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Beppu
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sekiguchi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwai
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Amino
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Ohwada
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Sakaida
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nakaseko
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kuwabara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016878:POEMS Syndrome / Q000097:blood* / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D012189:Retrospective Studies; D013792:Thalidomide / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide