scholarly journals Tumor-associated myeloid-derived suppressor cells as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 30-30
Author(s):  
Kalyan KUSUM Mukherjee ◽  
Sukanya Dhar ◽  
Rajib Bhattacharjee ◽  
Subhadip Das ◽  
Mohona Chakraborty ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Cells ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Large Cell ◽  
Potential Biomarker ◽  
Cellular Components

30 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: : Selected CD20+ DLBCL patients (n=51) were treated with 6-8 cycles of R-CHOP and included in the present study with their informed consent. A panel of immune cells, like, T (CD4+, CD8+)-cells, regulatory T (CD4+CD25+FoxP3)-cells, MDSCs (CD33+CD11b+CD14-/+), memory T (CD8+CD45RO+)-cells and multidrug resistance (MDR) phenotypes (P-gp, MRP1), were studied by flow-cytometry and RT-PCR at different phases of treatment. Results: Within 51 selected patients, 9 were disease free and 11 patients exhibited stable disease for 2 years following the completion of treatment. Rest of the patients (n=31) showed relapse in different time periods. Among several immune cells studied, CD33+CD11b+MDSCs were remarkably elevated in high-grade residual-and-relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14+ monocytic, but not CD33+CD14-granulocytic MDSCs were mostly increased in relapsed patients than control. Moreover, expression of MDR phenotypic markers was found to be elevated in these relapsed patients. Among relapsed patients CD8+CD45RO+ memory T cells were increased, however, these cells are mostly corrupted in nature. Conclusions: Observed correlation between increased monocytic MDSCs with the occurrence of residual disease and/or relapse suggests monocytic MDSCs might be a potential biomarker for prediction of residual-and-relapsed DLBCL patients.

Tumor-associated myeloid derived suppressor cells of granulocytic nature as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19040-e19040
Author(s):  
Kalyan Kusum Mukherjee ◽  
Sukanya Dhar ◽  
Mohona Chakraborty ◽  
Rajib Bhattacharjee ◽  
Shayani Bhanja ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Stable Disease ◽  
Immune Cells ◽  
Memory T Cells ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Potential Biomarker

e19040 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: 51 of selected pt.CD20+ DLBCL were treated with 6-8 cycles of R-CHOP and included in the present study. A panel of immune cells CD4+, CD8+ T cells, CD4+CD25+FoxP3 regulatory T cells, CD33+CD11b+CD14-/+ MDSCs and CD8+CD45RO+ Memory T cells were studied by flow-cytometry at different phases of treatment. Results: Within 51selected patients, 9 were disease free and 11patients exhibited stable disease for 2years (stable, non-relapsed, n = 20) following the completion of treatment. Rest of the patients (n = 31) showed relapse in different time periods within 2 years. Among several immune cells, CD33+CD11b+MDSCs were remarkably elevated in high grade residual and relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14- granulocytic, but not CD33+CD14+ monocytic MDSCs are mostly increased in relapsed patients than those having stable disease. CD4+CD25+FoxP3 regulatory T cells are also elevated in relapsed DLBCL patients, but increment is not comparable as MDSCs. No significant alteration was noticed in CD4+ and CD8+ T cells. Among relapsed patients CD8+CD45RO+ Memory T cells are increased, those are mostly corrupted in nature. Conclusions: Observed correlation between increased granulocytic MDSCs with the occurrence of residual disease and/or relapse suggests granulocytic MDSCs might be a potential biomarker for prediction of residual and relapse for DLBCL patients.

scholarly journals Long-Term Response and Possible Cure of Patients With B-Cell Malignancies With Dose-Escalated Rituximab

2017 ◽  
Vol 5 (1) ◽  
pp. 232470961769130
Author(s):  
Lauren M. Jacobs ◽  
Peter H. Wiernik ◽  
Janice P. Dutcher ◽  
Pablo Muxi
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Standard Dose ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Large Cell ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies

Rituximab (R), a chimeric monoclonal antibody targeting CD20 antigen on B-cells, has become a standard of care in the treatment of B-cell malignancies, most often in conjunction with cytotoxic chemotherapy. Activity has been demonstrated in many subtypes of B-cell lymphoma, including diffuse large cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), lymphocyte-predominant Hodgkin lymphoma, and Waldenström macroglobulinemia (WM). Additionally, dose escalation of R as a single agent has demonstrated improved activity in previously treated/poor prognosis CLL. We present 4 cases of B-cell malignancy (2 CLL variants/MCL, 1 FL, 1 WM) who received dose-escalated R as a single agent and achieved complete response (3 patients) and stable disease/partial response (1 patient) of 6.5+ to 15+ years duration. They have been off treatment for 6.5+ to 15+ years. Toxicity was minimal, with initial infusion reactions similar to those observed with standard dose infusions. There were no serious treatment-related adverse events or infections. Dose escalated R as a single agent may possibly be curative for some patients with B-cell malignancies, unlike the standard empiric dose of 375 mg/m2, and deserves further study.

scholarly journals Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients

2021 ◽  
Vol 10 (8) ◽  
pp. 1768
Author(s):  
Zhitao Wang ◽  
Rui Jiang ◽  
Qian Li ◽  
Huiping Wang ◽  
Qianshan Tao ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Pathological Process ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Accumulation Mechanism ◽  
Large B Cell

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.

Phase 3 trial (GCT3013-05) of epcoritamab versus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7569-TPS7569
Author(s):  
Catherine Thieblemont ◽  
Michael Roost Clausen ◽  
Anna Sureda Balari ◽  
Pier Luigi Zinzani ◽  
Christopher Fox ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Group Performance ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase 3 ◽  
Cycle Number ◽  
Car T ◽  
Anti Cd20

TPS7569 Background: Patients (pts) with DLBCL who are refractory to/or have relapsed (R/R) after treatment with chemotherapy and anti-CD20 monoclonal antibody (mAb) have a poor prognosis. There is a need for new treatment options to improve outcomes. Epcoritamab, a novel subcutaneous (SC) bispecific antibody, binds to CD3 on T-lymphocytes and CD20 on B-cell non-Hodgkin lymphoma (NHL) cells to induce potent and selective killing of malignant CD20+ B-cells. In an ongoing phase 1/2 dose-escalation trial in heavily pretreated pts with B-cell NHL (N = 68), epcoritamab demonstrated a tolerable safety profile and substantial single-agent anti-tumor activity, with a complete response (CR) rate of 55% and an overall response rate (ORR) of 91% in pts with R/R DLBCL (at ≥48 mg doses; n = 12) (NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable R/R DLBCL pts previously treated with chimeric antigen receptor T-cell (CAR-T) therapy achieved an objective response with 2 achieving CR. These encouraging data support the potential for epcoritamab to improve clinical outcomes in pts with R/R DLBCL. Here we describe the phase 3 trial of epcoritamab versus standard of care (SOC) treatments in pts with R/R DLBCL (NCT04628494). Methods: GCT3013-05 is a randomized, open-label, worldwide, multicenter, phase 3 study designed to evaluate the efficacy of epcoritamab versus investigator’s choice of SOC with R-GemOx (rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab) in adults with R/R disease of one the following CD20+ B-cell NHL histologies: I) DLBCL, not otherwise specified including de novo DLBCL or DLBCL histologically transformed from follicular lymphoma; II) “double-hit” or “triple-hit” DLBCL (high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations); or III) follicular lymphoma grade 3B. Other key eligibility criteria include: ≥1 line of prior chemotherapy that included treatment with an anti-CD20 mAb, Eastern Cooperative Oncology Group performance status 0–2, and prior failure of/ineligibility for autologous stem cell transplantation. Prior CAR-T therapy is allowed. A total of 480 pts will be randomized 1:1 to receive either SC epcoritamab at the recommended phase 2 dose (28-day cycles; weekly, biweekly, or monthly schedule depending on cycle number) until disease progression or unacceptable toxicity; or up to 4 cycles of biweekly treatment with intravenous (IV) R-GemOx (8 doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks). The primary endpoint is overall survival. Key secondary endpoints include progression-free survival, ORR, duration of response, time to response, and safety. The study is currently enrolling in Australia, Belgium, Denmark, France, Spain, and will open for enrollment in additional countries. Clinical trial information: NCT04628494.

Primary T-Cell–Rich B-Cell Lymphoma Masquerading as a Meningioma

2000 ◽  
Vol 124 (11) ◽  
pp. 1700-1703
Author(s):  
Barbara H. Amaker ◽  
Nitya R. Ghatak ◽  
Sean A. Jebraili ◽  
Andrea Ferreira-Gonzalez ◽  
Michael J. Kornstein
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Molecular Techniques ◽  
First Case ◽  
Dural Lymphoma ◽  
Immunohistochemical Techniques

Abstract Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case of T-cell–rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques.

Transformation of Monocytoid B-Cell Lymphoma to Large Cell Lymphoma Associated With Crystal-Storing Histiocytes

2000 ◽  
Vol 124 (3) ◽  
pp. 460-462
Author(s):  
Phataraporn Thorson ◽  
Jay L. Hess
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Lymph Node Biopsy ◽  
Lymphoid Cells ◽  
History Of ◽  
Cervical Lymph Node Biopsy ◽  
Large Cell Lymphoma ◽  
Monocytoid B Cell

Abstract We report a case of crystal-storing histiocytosis associated with large cell lymphoma in a patient with a history of monocytoid B-cell lymphoma 10 years previously. The cervical lymph node biopsy showed a diffuse proliferation of large lymphocytes with vesicular nuclear chromatin and distinct nucleoli. These lymphocytes were associated with numerous immunoglobulin λ light-chain crystal-storing histiocytes, which morphologically resembled rhabdomyoblasts. Occasional lymphoid cells also showed large immunoglobulin crystals. This case establishes the association of crystal-storing histiocytes with lymphomas of mucosa-associated lymphoid tissue and emphasizes the need for immunophenotyping to distinguish these unusual cases from other tumors, particularly adult rhabdomyomas.

Primary cutaneous B-cell lymphoma (low-grade, non large cell)

2007 ◽  
Vol 13 (1) ◽  
Author(s):  
Megan M Moore ◽  
Olympia I Kovich ◽  
Lance H Brown
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Low Grade ◽  
Cutaneous B Cell Lymphoma

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

1997 ◽  
Vol 15 (4) ◽  
pp. 1654-1663 ◽  
Author(s):  
D Wendum ◽  
C Sebban ◽  
P Gaulard ◽  
B Coiffier ◽  
H Tilly ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Intensive Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Beta 2 Microglobulin

PURPOSE The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

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