title: Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma.
abstract: To evaluate the prognostic impact of minimal residual disease (MRD), quantitative real-time polymerase chain reaction (RQ-PCR) of clonal IGH rearrangements was performed in 29 patients with mantle cell lymphoma (MCL) treated with high-dose radiochemotherapy and autologous stem cell transplantation (ASCT). Fourteen of 27 patients evaluable for MRD after ASCT achieved complete clinical and molecular remission, whereas 13 patients had detectable MRD within the first year after ASCT. Molecular remission after ASCT was strongly predictive for improved outcome, with a median progression-free survival (PFS) of 92 months in the MRD-negative group compared with 21 months in the MRD-positive group (P < .001). Median overall survival (OS) was 44 months in the MRD-positive group and has not been reached in the MRD-negative group (P < .003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (P = .001 and P = .021, respectively). While cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP)-like cytoreduction had only modest influence, ara-C-containing mobilization and myeloablative radiochemotherapy significantly reduced MRD. Quantitative MRD measured in the stem cell products of 27 patients was not predictive for molecular remission. We conclude that sequential quantitative monitoring of residual disease after ASCT is a powerful indicator for treatment outcome in MCL and defines subgroups of patients with a significantly different prognosis.
authors.affiliation: Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Chemnitzstr 33, 24116 Kiel, Germany. c.pott@med2.uni-kiel.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Carsten
authors.initials: C
authors.lastname: Schrader
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Raff
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.forename: Benedikt
authors.initials: B
authors.lastname: Gahn
authors.forename: Michael
authors.initials: M
authors.lastname: Unterhalt
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008722:Methods; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome