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.