Bone Marrow Histopathological and Molecular Changes of Small B-Cell Lymphomas after Rituximab Therapy: Comparison with Clinical Response and Patients' Outcome

Abstract

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology - follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL) - was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

Mantle cell lymphoma with flow cytometric evidence of clonal plasmacytic differentiation: A case report

“…However, distinguishing MCL with PC differentiation from MCL with a concurrent but unrelated plasma cell dyscrasia may have treatment implications. Furthermore, other B-cell lymphomas with PC differentiation have been reported to show post-treatment relapses with only PC histology (19,20). The distinctive phenotype of the plasma cells in this case, with coexpression of CD5 and CD19, renders flow cytometry immunophenotyping of great value in evaluating possible relapses that show only PC histology.…”

Involvement of NK Cells against Tumors and Parasites

“…It was also shown that NK cells from non-immune individuals can kill plasmodia-infected erythrocytes in the absence of opsonizing antibodies directly through cell-cell interaction, and that this activity was inhibited by anti-FAS antibody and granzyme B inhibitor (55). Furthermore, the finding of children with acute P. falciparum infection suggested a positive correlation between the lytic activity of natural killer cells towards the human leukemia line k562 ex vivo and the extent of parasitemia, and provided evidence that purified NK cells from both healthy and P. falciparum-infected individuals directly lyse parasitized erythrocytes in vitro (56)(57)(58)(59)(60)(61)(62). This optimal activation of NKderived IFN-γ production in vitro requires contact between NK cells and P. falciparum-infected erythrocytes (53).…”

B-cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, without the development of Richter's Syndrome, with Neoplastic Cells Lacking CD20 Antigen Expression after Rituximab Treatment

“…Furthermore, the bone marrow neoplastic cells were positive for CD5, CD19 ( Figure 3C), CD23, CD25, and λ-chain of immunoglobulin light chain and negative for not only CD3 and CD10, but also for CD20 ( Figure 3D), which was found to be positive at the initial diagnosis ( Figure 3B) by the cell surface marker analysis using flow cytometry. Complicated chromosomal abnormalities including abnormalities in chromosomes 3,6,7,8,9,13,15,16,17, and 19, were detected in 15 of 20 analyzed BMCs by the G-banding method. The abnormalities in chromosome 11, which were detected at the initial diagnosis, were not included.…”

“…We ultimately concluded that the neoplastic B-CLL/SLL cells lost the expression of the CD20 antigen after the rituximab treatment. a small number of cases have been reported thus far [9,[12][13][14][15]. The characteristics of 11 patients (including 6 males) whose details were described are listed in Table 2.…”

“…D' Auria et al [9] reported that 4 of 8 (50%) tested CLL/SLL patients demonstrated CD20 antigen loss, half of whom later developed RS. Goteri et al [13] Several mechanisms for the loss of CD20 antigen expression on the neoplastic cells have been demonstrated in patients with B-CLL/ SLL receiving rituximab therapy. Jilani et al [16] tested the presence of rituximab on the surface of CLL lymphocytes using anti-mouse immunoglobulin antibodies to detect rituximab and found its presence in 3 of 65 B-CLL patients, despite the fact that most of them had no detectable CD20 expression.…”