title: Role of the molecular staging and response in the management of follicular lymphoma patients.
abstract: Bcl-2/IgH rearrangement is the molecular hallmark of follicular lymphoma which is present in 70 - 90% of cases at diagnosis. The significance of the bcl-2 rearrangement at onset of disease and of its clearing after treatment (molecular response) is still controversial. The aims of the present analysis are: to evaluate the incidence of bcl-2 rearrangement in blood and marrow in a cohort of patients systematically investigated at diagnosis, to describe the correlation between bcl-2 and presenting features, to clarify the correlation of molecular response with outcome. Of 98 patients studied at initial staging for the presence of bcl-2 rearrangement, 64 (65%) showed bcl-2/IgH rearrangement in peripheral blood (PB) and/or bone marrow (BM) (58 at Major Breakpoint Region, MBR, and 6 at minor cluster region, mcr) while no bcl-2/IgH rearrangement was detected in the remaining 34 (35%) (germline status). No statistically significant differences were found between bcl-2 positive and bcl-2 negative cases as concerns presenting clinical features and response to first-line therapy. The median event-free survival, EFS, was not reached for the bcl-2 negative patients in PB and was 11 months for bcl-2 positive patients (statistically significant, P = 0.01) and, similarly, the median EFS was not reached for the bcl-2 negative patients in BM and was 11 months for bcl-2 positive patients (statistically significant, P = 0.04). Of the 64 bcl-2 positive cases, patients were analysed for molecular response (48 in BM and 40 in PB): 16 were molecular responders in BM and 20 were molecular responders in PB. The median EFS was 19 months for molecular responders in PB and 9 months for non-responders; 1-year-EFS was 68% (95% CI; 49 - 88), for responders in PB and 42% (95% CI; 22 - 61) for non-responders (P = 0.05). The median EFS was 11 months both for molecular responders and non-responders in BM; 1-year-EFS was 52% for responders in BM (CI; 30 - 73), and 43% (CI 33 - 71) for non-responders (P = 0.7). No clinical feature showed significant correlation with PB and BM molecular responses. This analysis shows that bcl-2 rearrangement in blood and bone marrow is frequently detected at staging, even in stage I disease. Absence of the bcl-2 rearrangement is related to a better EFS and the achievement of a molecular response in peripheral blood after therapy is associated with a better EFS.
authors.affiliation: Division of Hematology, IRCCS Policlinico San Matteo, University of Pavia, Italy. luca.arcaini@unipv.it
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Nora
authors.initials: N
authors.lastname: Colombo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Silvia
authors.initials: S
authors.lastname: Calatroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Ester
authors.initials: E
authors.lastname: Orlandi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bonfichi
authors.forename: Sara
authors.initials: S
authors.lastname: Burcheri
authors.forename: Matteo Della
authors.initials: MD
authors.lastname: Porta
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Francesca
authors.initials: F
authors.lastname: Montanari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Algarotti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2