Abstract
Introduction: Multidimensional flow cytometry (MFC) has not yet shown a high clinical value in patients with diffuse large B-cell lymphoma (DLBCL), probably due to the phenotypic heterogeneity of these lymphomas. In the present study, we have evaluated bone marrow (BM) infiltration in patients with DLBCL using MFC with the following objectives: 1) evaluating its prognostic impact compared to other techniques such as histology or PET; 2) determine the specific phenotypic pattern of the tumor cell of each patient for subsequent follow-up of minimal residual disease (MRD) after treatment. Methods: We centrally evaluated BM samples from patients included in the multicenter randomized phase 2 clinical trial GEL-R-COMP-2013 (EudraCT: 2013-001065-17), that compares R-CHOP versus R-COMP in patients with newly diagnosed DLBCL or follicular lymphoma (FL) grade 3b. High resolution (8 colors) and high sensitivity (more than 1 million cells analyzed) direct immunofluorescence techniques were used, following the protocols defined by EuroFlow. An automatic analysis was carried out in addition to the manual analysis, using the Compass III tool, available in the Infinicyt analysis software (Cytognos, S.L.). Results: From a total of 91 patients included in the clinical trial, 54 participated in the present study (48 DLBCL and 6 FL grade 3b). The median age was 75 years (61-86). BM infiltration was detected by MFC in 20 patients (37%) at diagnosis and 0 out of 13 at post-treatment evaluation. Regarding the phenotypic characterization, concordant BM infiltration by DLBCL was detected in only 6 cases. In contrast, discordant infiltration was detected in 14 (70%) patients, with a very heterogeneous phenotype: 3 low grade FL, 2 chronic lymphocytic leukemia, 5 marginal zone lymphoma and 4 small cell lymphoma with non-specific phenotype. Molecular studies showed monoclonal rearrangements in 14 out of 17 (82.3%) samples tested. Preliminary analysis of the prognostic impact of BM infiltration by MFC is shown in Table 1. The presence of concordant BM infiltration was associated with worse survival, although the differences were not statistically significant, possibly due to the low number of cases. On the other hand, discordant BM infiltration had no significant prognostic influence. Conclusions: High resolution MFC allowed the detection of small clonal populations in BM in a very high proportion of patients with newly diagnosed DLBCL. In most cases, infiltration was discordant with tumor histology and, apparently, had no prognostic relevance. MRD was not detected in any of the cases. We plan to correlate MFC findings with those of histology and PET, also centrally reviewed, as well as to perform molecular studies on lymph node and BM samples to assess their clonal relationship. Keywords: diffuse large B-cell lymphoma (DLBCL); flow cytometry. Disclosures: Sancho, J: Honoraria: Roche, Janssen, Gilead, Khen Fharma, Celgene, Sanofy, Servier, Mundipharma; Research Funding: Gilead. Martín, A: Consultant Advisory Role: Celgene, Roche.; Honoraria: Celgene, Roche, Servier, Janssen.
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