title: Increase in minimal residual disease in peripheral blood before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy.
abstract: BACKGROUND
  We developed previously a minimal residual disease (MRD) monitoring system in dogs with lymphoma by exploring a highly sensitive real-time PCR system.
  
  
  OBJECTIVE
  To identify the change in MRD before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy.
  
  
  METHODS
  Twenty dogs with multicentric high-grade B-cell lymphoma.
  
  
  METHODS
  MRD levels in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR amplifying the rearranged immunoglobulin heavy chain gene. MRD measurement and clinical assessment were performed every 2-4 weeks for 28-601 days after completion of chemotherapy. An increase in MRD was defined as an increase by more than 0.5, calculated by log₁₀ [copy number of MRD per 10⁵ PBMCs], based on the uncertainty level observed in a canine lymphoma cell line.
  
  
  RESULTS
  During the follow-up period, 15 dogs relapsed in 28-320 days (median, 120 days) after completion of chemotherapy. An increase in MRD was detected 2 weeks or more before relapse in 14 of the 15 dogs, but an increase in MRD before relapse could not be detected in the remaining 1 dog. The time from increased MRD to clinical relapse was 0-63 days (median, 42 days). In contrast, no increase in MRD was detected in 5 dogs that did not experience clinical relapse.
  
  
  CONCLUSIONS
  An increase in MRD can be detected before clinical relapse in dogs with lymphoma. Application of early reinduction therapy based on an increase in MRD before clinical relapse may improve treatment outcome in canine lymphoma.
authors.affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Goto-Koshino
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujino
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004283:Dog Diseases / Q000175:diagnosis* / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy / Q000662:veterinary; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy / Q000662:veterinary; D016133:Polymerase Chain Reaction / Q000662:veterinary*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D007143:Immunoglobulin Heavy Chains