Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

Abstract

The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.

Diagnostic Accuracy and Prognostic Relevance of Immunoglobulin Heavy Chain Rearrangement and 18F-FDG-PET/CT Compared With Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Patients With Diffuse Large B-Cell Lymphoma

“…Compared with previous studies, the study similarly found that the clinical characteristics of concordant mBMI were associated with poor ECOG performance status, high-intermediate standard, and NCCN-IPI risks, compared with the discordant morphologic marrow involvements. 37 38 39 Complete response (CR) was achieved in all three patients with discordant mBMI, however, half of patients with concordant mBMI failed to achieve a CR after R-CHOP chemotherapy. All three patients with discordant atypical morphology or focal marrow invasion had IgH rearrangement.…”

Combination of Bone Marrow Biopsy and Flow Cytometric Analysis: The Prognostically Relevant Central Approach for Detecting Bone Marrow Invasion in Diffuse Large B-Cell Lymphoma

“…Finally, one of the conceivable limitations in this study is the lack of consideration for or observation of concordant BM disease defined by the involved BM area consisting of mostly large noncleaved lymphoma cells and discordant BM disease defined by the involved BM consisting of mostly small low-grade lymphoma cells in DLBCL [ 36 , 37 , 38 ]. It has been reported that the subclassification of invaded lymphoma cells into two morphologically distinct types, i.e., concordant and discordant types, is associated with prognosis [ 36 , 37 , 38 ]. However, we could not evaluate this point because pathologists reported no discordant BM involvement with BM biopsy or BM clot assessment in our study.…”

“…However, we could not evaluate this point because pathologists reported no discordant BM involvement with BM biopsy or BM clot assessment in our study. Considering discordant clonal lymphoid cells occasionally reflects the incidental co-occurrence of indolent clonal lymphoid proliferation with DLBCL [ 36 , 37 ], one of the conceivable reasons which underlay the discrepancy between frequent discordant BM involvement in previous reports and the absence of discordant BM disease in our cohort may be the distinct racial impact on the frequency of indolent B cell neoplasms, such as follicular lymphoma, chronic lymphoid leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL). For instance, the incidence of CLL was about 5–10 folds less in Asians than in Caucasians [ 39 , 40 ], and this was also the case with MBL [ 41 ].…”

Diagnostic accuracy of pelvic magnetic resonance imaging for the assessment of bone marrow involvement in diffuse large B-cell lymphoma

“…BMinv is a common occurrence in lymphoma. A recent study [ 19 ] revealed that patients with BMinv in DLBCL had a higher risk of central nervous system recurrence and a lower progression-free survival; therefore, timely and accurate diagnosis of lymphoma BMinv is important for disease staging, choosing treatment options, and evaluating the prognosis. Current methods for clinical evaluation of BMinv in lymphoma include BMB, PET/CT, and whole-body MRI [ 11 , 20 ].…”