CONCORDANT BONE MARROW INVOLVEMENT MAINTAINS AN ADVERSE PROGNOSTIC SIGNIFICANCE IN PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA TREATED WITH R-CHOP.

Background: The improvement in treatment outcomes of diffuse large B-cell lymphoma (DLBCL) observed following the introduction of Rituximab has altered previous views about risk assessment. Approximately 10% to 25% of patients (pts) with DLBCL exhibit bone marrow involvement with lymphoma at the time of diagnosis. Concordant bone marrow involvement has generally been associated with a poorer outcome but the impact of discordant involvement remains less clear. The aim of this study was to examine the prognostic impact of (BM) involvement on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 178 patients with de novo DLBCL. Patients and methods: Between 2000 and 2010 we retrospectively analyzed 178 untreated DLBCL pts, newly diagnosed at our centre, with or without (BM) involvement. The median age was 59 yrs (16-89 yrs), 109 (61%) were males, 75 (43%) had B symptoms, 27 (15%) had extranodal dissemination >1, 49 (28%) had a high IPI score. The treatment protocol for front-line therapy included rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Progression-free (PFS) and overall survival (OS) were calculated according to the absence or presence of (BM) involvement and the presence of histological discordance or concordance between the primary site and the bone marrow. Results: A total of 41 (23%) of 178 pts had bone marrow involvement, concordant in 16 (9%) and discordant in 25 (14%). Median follow-up was 30 months (range, 1 to 120). The 41 pts with bone marrow involvement had a poorer prognosis compared with the group without (3 year progression-free survival, 56% vs 81% - p<0.05).) PFS was inferior in those with concordant (p<0.001) and discordant (p<0.05) involvement, while OS was inferior only in those with concordant involvement (p<0.001). Concordant involvement was associated with elevated lactate dehydrogenase, extranodal dissemination>1, IPI>2, performance status >2 and elevated beta 2 microglobulins. Complete remission (CR) rates were inferior in concordant bone marrow involvement as compared to discordant or no involvement (48% vs 59% vs 64%). Conclusion: Our data show that concordant, but not discordant bone marrow involvement, could represent a possible predictive factor of poor prognosis, which would help to identify a high risk subgroup of newly diagnosed DLBCL. To confirm these results, further large-scale and prospective studies will be required.