The impact of structural factors on diagnostic delay in diffuse large B‐cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

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Diffuse large B-cell lymphoma mimicking chronic osteomyelitis of the ankle joint: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x20987339 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2098733

Author(s):

Emam M Kheder ◽

Hussain H Sharahlii ◽

Saad M AlSubaie ◽

Mushref A Algarni ◽

Hussain Al Omar

Keyword(s):

Case Report ◽

B Cell ◽

Ankle Joint ◽

Chronic Osteomyelitis ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Chronic Infections ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Lymphoma is the seventh most common type of malignancy in both males and females. It may develop in any location where lymphomatous tissue exists. Although extranodal presentation in the lower limb and pelvis are uncommon, it could present with diverse manifestations. We report an unusual case of primary extranodal large B-cell lymphoma of the ankle joint initially presumed to be a chronic osteomyelitis. This case report discusses the impact of imaging studies on decision-making and highlights the need to consider malignancy in chronic infections.

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The Role of Transplantation in Diffuse Large B-Cell Lymphoma: The Impact of Rituximab Plus Chemotherapy in First-line and Relapsed Settings

Current Hematologic Malignancy Reports ◽

10.1007/s11899-010-0075-5 ◽

2010 ◽

Vol 6 (1) ◽

pp. 47-57 ◽

Cited By ~ 4

Author(s):

Celso Arrais Rodrigues ◽

Poliana Alves Patah ◽

Yana A. S. Novis ◽

Chitra Hosing ◽

Marcos de Lima

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

First Line ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

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Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

Leukemia & Lymphoma ◽

10.3109/10428194.2012.698739 ◽

2012 ◽

Vol 54 (1) ◽

pp. 83-89 ◽

Cited By ~ 9

Author(s):

Tanin Intragumtornchai ◽

Udomsak Bunworasate ◽

Noppadol Siritanaratkul ◽

Archrob Khuhapinant ◽

Weerasak Nawarawong ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Universal Coverage ◽

Free Survival ◽

Large B Cell Lymphoma ◽

The Impact ◽

Universal Coverage Scheme ◽

Large B Cell

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Osteopontin expression and its relationship with prognostic factors in diffuse large B-cell lymphoma

Hematology Reports ◽

10.4081/hr.2019.7964 ◽

2019 ◽

Vol 11 (3) ◽

Author(s):

Gilberto Barranco ◽

Edith Fernández ◽

Silvia Rivas ◽

Roxana Quezada ◽

Dolores Nava ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Germinal Center ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cox Proportional Hazards ◽

Biological Behavior ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

The aim of this study is to explore the expression of osteopontin (OPN) and its relationship with prognostic factors and survival in diffuse large B cell lymphoma (DLBCL). A tissue microarray was performed for immunohistochemical evaluation. Contingency tables were analyzed for trends; chi-square test was used to determine differences between groups. Univariate and multivariate Cox proportional hazards-regression analyses were performed to evaluate the impact of prognostic factors on survival. Expression of OPN was observed in 28%. It was different in non-germinal center DLBCL (P=0.04). The mean overall survival (OS) was lower in patients with positive OPN expression (19.762; CI 95% 14.269-25.255) it was not significant (P=0.123). It is not possible to establish a clear relationship between the expression by immunohistochemistry of osteopontin and a poor prognosis but it would be important to complement the analysis with other techniques as PCR or NGS that allow us to assess the influence of the isoforms and post-translational modifications of OPN on the biological behavior of DLBCL. Our findings indicate that OPN expression could be associated with a more aggressive variant of lymphoma: non-germinal center DLBCL.

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Diffuse Large B-Cell Lymphoma Classification System That Associates Normal B-Cell Subset Phenotypes With Prognosis

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.7080 ◽

2015 ◽

Vol 33 (12) ◽

pp. 1379-1388 ◽

Cited By ~ 52

Author(s):

Karen Dybkær ◽

Martin Bøgsted ◽

Steffen Falgreen ◽

Julie S. Bødker ◽

Malene K. Kjeldsen ◽

...

Keyword(s):

B Cell ◽

Classification System ◽

Cell Lymphoma ◽

Positive Impact ◽

Cell Subset ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.

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Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2017.73.2784 ◽

2017 ◽

Vol 35 (31) ◽

pp. 3538-3546 ◽

Cited By ~ 77

Author(s):

John P. Leonard ◽

Kathryn S. Kolibaba ◽

James A. Reeves ◽

Anil Tulpule ◽

Ian W. Flinn ◽

...

Keyword(s):

B Cell ◽

Germinal Center ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Germinal Center B Cell ◽

The Impact ◽

Large B Cell

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

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FcγRIIIa Gene Polymorphisms May Correlate with Response to Frontline R-CHOP Therapy for Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.2457.2457 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2457-2457

Author(s):

Dong Hwan Kim ◽

Hee Du Jung ◽

Sang Kyun Sohn ◽

Je-Jung Lee ◽

Deok-Hwan Yang ◽

...

Keyword(s):

B Cell ◽

Gene Polymorphisms ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Effector Cells ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell ◽

Chop Therapy

Abstract Background: The precise mechanism of rituximab (R) plus CHOP (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2 mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via IgG fragment C receptors (FcR), was also proposed as a mechanism of Rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect R’s affinity for ADCC effector cells. Patients and Methods: The FcγRIIIa and FcγRIIa gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n=113) comparing to CHOP therapy (n=85). Results: The FcγRIIIa valine (V) allele was significantly correlated with higher complete response rate to R-CHOP compared to phenylalalnine (F) allele (88% in V/V versus 79% in V/F versus 50% in F/F, p=0.002), while no difference was found between FcγRIIa polymorphism. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of FcγRIIIa gene polymorphism on response rate was not noted in CHOP group. In terms of overall or event-free survival, no difference was found according to FcγRIIIa or FcγRIIa alleles. Conclusion: The FcγRIIIa SNP is predictive of response to R-CHOP, but does not correlate with survival in DLBCL patients.

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