title: Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes.
abstract: OBJECTIVE
  To evaluate the prognostic relevance of molecular monitoring of minimal residual disease in indolent lymphomas receiving high-dose sequential chemotherapy and autografting.
  
  
  METHODS
  A polymerase chain reaction- (PCR-)based strategy was used to evaluate the presence of residual tumor cells in a panel of 70 indolent lymphoma patients: 40 with follicular (FCL), 14 with small lymphocytic (SLL), and 16 with mantle-cell (MCL) lymphomas. They were treated either with first-line (n = 61) or second-line (n = 9) therapy with an intensified high-dose chemotherapy program followed by peripheral-blood progenitor cells autografting. The Bcl-1, Bcl-2, and immunoglobulin gene rearrangements were used as lymphoma-specific markers. Overall, a molecular marker was obtained from the diagnostic tissue in 60 of 70 patients (86%). Results The collection of PCR-negative cells and the achievement of posttransplantation molecular remission (MR) were common in patients with FCL subtype (54% and 70%, respectively), whereas they were not frequent among SLL and MCL (25% and 12.5%, respectively) patients. With a median molecular follow-up of 75 months, an 88% incidence of relapse was observed among patients never attaining MR. In contrast, relapse incidence was only 8% among patients attaining a durable MR (P <.005). At present, 26 patients (20 with FCL and six with non-FCL) are long-term survivors in absence of clinical and molecular disease.
  
  
  CONCLUSIONS
  Our results indicate that among indolent lymphomas, FCL and non-FCL subtypes show a significantly different behavior in terms of MR achievement, and MR after intensive chemotherapy and autografting is predictive for a prolonged disease-free survival, whereas persistent PCR positivity is associated with a high risk of relapse.
authors.affiliation: U.O. Ematologia-Trapianto Midollo Osseo, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. paolo.corradini@istitutotumori.mi.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Francesco
authors.initials: F
authors.lastname: Zallio
authors.forename: Monica
authors.initials: M
authors.lastname: Astolfi
authors.forename: Elena
authors.initials: E
authors.lastname: Rizzo
authors.forename: Selina
authors.initials: S
authors.lastname: Sametti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cuttica
authors.forename: Rosalba
authors.initials: R
authors.lastname: Rosato
authors.forename: Lucia
authors.initials: L
authors.lastname: Farina
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pileri
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy; D008224:Lymphoma, Follicular / Q000628:therapy; D020522:Lymphoma, Mantle-Cell / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D018365:Neoplasm, Residual / Q000628:therapy; D016133:Polymerase Chain Reaction; D014182:Transplantation, Autologous
chemical_list: D014408:Biomarkers, Tumor