title: Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC).
abstract: BACKGROUND
  Circulating myeloma cells (CMC), exhibiting the same immunoglobulin heavy-chain gene rearrangements as the plasma cells, are part of the myeloma clone. In this study, we evaluated the effect of idiotype (Id) vaccination on CMC.
  
  
  METHODS
  Eleven patients were immunized with the autologous Id in combinations with granulocyte-macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id-specific T cells were monitored by proliferation assay, enzyme-linked immunospot (interferon-gamma) assay, and quantitative real-time PCR for cytokines. Regulatory T (T(reg)) cells were analyzed by flow cytometry.
  
  
  RESULTS
  CMC were detected in 9 of 11 patients at start of vaccination. In four patients, CMC declined and two had a complete molecular remission. Further two patients had stable levels of CMC during follow-up, while in three patients CMC progressively increased. Six patients had a vaccine-induced Id-specific T-cell response. A significant correlation was observed between reduced/stable levels of CMC and the Id-specific T cells (P < 0.02). The frequency of T(reg) cells was decreased in immune responders, but increased in immune nonresponders (P < 0.05). No significant change in the serum M-protein concentration was, however, observed in any patient.
  
  
  CONCLUSIONS
  Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells. Further studies are warranted to analyze the clinical significance of CMC and clinical effects of Id vaccination.
authors.affiliation: Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Stockholm, Sweden.
authors.forename: A O
authors.initials: AO
authors.lastname: Abdalla
authors.forename: P
authors.initials: P
authors.lastname: Kokhaei
authors.forename: L
authors.initials: L
authors.lastname: Hansson
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.forename: A
authors.initials: A
authors.lastname: Osterborg
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor