Role of the molecular staging and response in the management of follicular lymphoma patients

• Published in: Leukemia & lymphoma Vol. 47; no. 6; pp. 1018 - 1022
• Main Authors: Arcaini, Luca, Colombo, Nora, Bernasconi, Paolo, Calatroni, Silvia, Passamonti, Francesco, Orlandi, Ester, Bonfichi, Maurizio, Burcheri, Sara, Della Porta, Matteo, Rumi, Elisa, Montanari, Francesca, Algarotti, Alessandra, Pascutto, Cristiana, Lazzarino, Mario
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.06.2006; Taylor & Francis
• Subjects: Aged; bcl-2; Bone Marrow Cells - metabolism; Disease-Free Survival; Female; Follicular lymphoma; Gene Rearrangement; Humans; Lymphoma, Follicular - diagnosis; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - therapy; Male; Middle Aged; molecular response; Neoplasm Staging - methods; Prognosis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Remission Induction; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190500467834

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.