title: Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: the FIL FOLL05 trial.
abstract: OBJECTIVE
  The role of the minimal residual disease (MRD) in follicular lymphoma is still debated. In this study, we assessed whether the BCL2/IGH rearrangement could have a prognostic role in patients receiving R-CHOP, R-FM, or R-CVP.
  
  
  METHODS
  DNAs from 415 patients among the 504 cases enrolled in the FOLL05 trial (NCT00774826) were centralized and assessed for the BCL2/IGH at diagnosis, at the end of treatment, and after 12 and 24 months.
  
  
  RESULTS
  At diagnosis, the molecular marker was detected in 53% of cases. Patients without molecular marker or with a low molecular tumor burden (<1 × 10(-4) copies) showed higher complete remission (CR) rate and longer progression-free survival (PFS; 3-year PFS 80% vs. 59%; P = 0.015). PFS was significantly conditioned by the PCR status at 12 and 24 months, with 3-year PFS of 66% for MRD(-) cases versus 41% for those MRD(+) at 12 months (P = 0.015), and 84% versus 50% at 24 months (P = 0.014). The MRD negativity at 12 and 24 months resulted in an improved PFS both in CR and in partial remission (PR) patients (3-year PFS = 72% for cases CR/PCR(-) vs. 32% for those CR/PCR(+) vs. 62% for those PR/PCR(-) and 25% for patients in PR/PCR(+); P = 0.001). The prognostic value of MRD at 12 and 24 months of follow-up was confirmed also in multivariate analysis.
  
  
  CONCLUSIONS
  In this study, standardized molecular techniques have been adopted and applied on bone marrow samples from a large cohort. Data reported show that the MRD detection is a powerful independent predictor of PFS in patients with follicular lymphoma receiving conventional chemoimmunotherapy.
authors.affiliation: Department of Clinical and Experimental Medicine - University of Pisa, Pisa, Italy. sara.galimberti@med.unipi.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Galimberti
authors.affiliation: Department of Diagnostic, Clinics and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.affiliation: Department of Clinical and Experimental Medicine - University of Pisa, Pisa, Italy. GenOMec School of University of Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ciabatti
authors.affiliation: Department of Clinical and Experimental Medicine - University of Pisa, Pisa, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Grassi
authors.affiliation: Department of Clinical and Experimental Medicine - University of Pisa, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guerrini
authors.affiliation: Department of Diagnostic, Clinics and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dondi
authors.affiliation: Department of Diagnostic, Clinics and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.affiliation: Hospital of Science and Health City, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.affiliation: Department of Experimental, Diagnostic, and Speciality Medicine, Bologna University, Bologna, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.affiliation: Department of Experimental, Diagnostic, and Speciality Medicine, Bologna University, Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gazzola
authors.affiliation: Department of Experimental, Diagnostic, and Speciality Medicine, Bologna University, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mannu
authors.affiliation: Hospital of Science and Health City, Turin, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Monitillo
authors.affiliation: Hospital of Science and Health City, Turin, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantoan
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Della Starza
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Cavalli
authors.affiliation: Department of Oncology and Hematology, IRCSS "San Matteo", University of Pavia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.affiliation: Hematology Unit, Hospital of Brescia, Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tucci
authors.affiliation: Hematology Unit, "Ferrarotto" Hospital, Catania, Italy.
authors.forename: Giuseppe Alberto
authors.initials: GA
authors.lastname: Palumbo
authors.affiliation: Hematology Unit, AO Careggi, Florence, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Rigacci
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.affiliation: Hospital of Science and Health City, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.affiliation: Hospital of Science and Health City, Turin, Italy.
authors.forename: Carola
authors.initials: C
authors.lastname: Boccomini
authors.affiliation: Hematology Unit, Piacenza Hospital, Piacenza, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vallisa
authors.affiliation: Hematology Unit, Merano Hospital, Merano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertoldero
authors.affiliation: SCDU Hematology, Department of Translational Medicine, University of East Piedmont, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Scientific Direction, IECCS, Referral Cancer Center of basilicata, Rionero In vulture (Pz), Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Department of Clinical and Experimental Medicine - University of Pisa, Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.affiliation: Department of Diagnostic, Clinics and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D018628:Gene Dosage; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains