title: Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909.
abstract: BACKGROUND
  In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial.
  
  
  METHODS
  Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression.
  
  
  RESULTS
  Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis.
  
  
  CONCLUSIONS
  Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma.
authors.affiliation: University of Chicago Medical Center 5841, S. Maryland Ave, MC2115 Chicago, IL 60637, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Greg
authors.initials: G
authors.lastname: Koval
authors.forename: Greg
authors.initials: G
authors.lastname: Malnassy
authors.forename: Dorie
authors.initials: D
authors.lastname: Sher
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Damon
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Donna Marie
authors.initials: DM
authors.lastname: Bucci
authors.forename: Charles A
authors.initials: CA
authors.lastname: Linker
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D060828:Induction Chemotherapy; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual; D011379:Prognosis; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
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