scholarly journals A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes

2019 ◽  
Vol 53 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Chrishanthi Rajasooriyar ◽  
Jeremy Tey ◽  
Lea Choung Wong ◽  
Michelle Poon ◽  
Rao Nandini ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

scholarly journals Triple-negative diffuse large B-cell lymphoma: A distinct entity

2021 ◽  
Vol 12 (4) ◽  
pp. 427-429
Author(s):  
Yasmine Slimani ◽  
Fouzia Hali ◽  
Fatima-Zohra El Fatoiki
Keyword(s):  
B Cell ◽  
Triple Negative ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Positive Staining ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The Hans algorithm categorizes the diffuse large B-cell lymphoma (DLBCL) into two major subtypes: the germinal center B-cell-like (GCB) DLBCL and the non-GCB DLBCL. This classification is based on three immunohistochemical markers: CD10, BCL6, and MUM1. The non-GCB subtype is associated with lower overall survival (OS) and progression-free survival (PFS) rates compared to the GCB. DLBCL without positive staining for these three markers (CD10–, BCL6–, MUM1–), also called a triple negative or TN, are classified as the non-GCB subtype. However, they show different clinical characteristics and better prognosis than others assigned to the same cell-of-origin group. Herein, we report a case of a TN non-GCB DLBCL with a complete response after R-CHOP therapy. Together with previous reports of TN non-GCB DLBCLs, our case might depreciate the prognostic value of the Hans algorithm, which was already controversial in the literature, especially in the chemoimmunotherapy era.

scholarly journals Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India

2021 ◽  
Vol 11 ◽  
Author(s):  
Ajay Gogia ◽  
Sukesh Nair ◽  
Shalabh Arora ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
...  
Keyword(s):  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Ecog Performance Status ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p &lt; 0.001), age &gt;60 years (p = 0.001), bulky disease (p &lt; 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p &lt; 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

Treatment of Primary Mediastinal Large B-Cell Lymphoma with Immunochemotherapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4749-4749
Author(s):  
Jacques Tabacof ◽  
Novis A.S. Yana
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
Autologous Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Small Series ◽  
Large B Cell

Abstract Background: Primary mediastinal large B-cell (PMLBCL) non-Hodgkin’s lymphoma (NHL) is a relative rare disease and represents less than 2% of all newly diagnosed NHL. Analyses with DNA microarrays verified that primary mediastinal and diffuse large B-cell lymphomas are different diseases. The optimal treatment is still undefined. The aim of this study is to evaluate the response to immunochemotherapy in 10 cases of PMLBCL. Patients and Methods: 10 previously untreated patients with confirmed diagnosis of PMLBCL were enrolled in 2 different institutions. All the patients were treated with rituximab (R) plus polychemotherapy. We retrospectively analysed their clinical data and response to immunochemotherapy. Results: median age was 37 years-old (range 18 to 45 years), 5 were male and 5 were female, 6 had bulky disease, 4 had B symptoms and 4 presented HDL elevated. The immunochemotherapy regimens utilized for treatment were: 3 R+MACOP-B, 5 R+CHOP, 1 R+CBV and 1 R+MACOP-B+ICE+BEAM. Complete remission was obtained in 9 patients (90%) and no relapse was observed in this group. One patient died 7 months after ABMT. Three out of 10 patients who were chemosensitive underwent Autologous Bone Marrow Transplantation (ABMT). Median disease free survival was 22 months. One patient got pregnant 4 months after the 8th cycle of R+CHOP, when she was in complete remission. The patient was delivered of a healthy child and is in complete remission for 34 months. It was observed toxicities related to chemotherapy. There was no report of toxicities during and after rituximab infusion. Conclusion: the addition of rituximab to polychemotherapy may be a good strategy to the management of primary mediastinal large-B cell lymphoma. In this small series there was a high rate of complete sustained response. However, larger randomized studies are needed to confirm these findings.

Fostamatinib for the treatment of diffuse large B-cell lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20067-e20067
Author(s):  
Hendrik-Tobias Arkenau ◽  
Anna Patrikidou ◽  
Ian Flinn ◽  
Jonas C. Hylton ◽  
Sandra Tong ◽  
...  
Keyword(s):  
Partial Response ◽  
B Cell ◽  
Clinical Benefit ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Intermediate Cell ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e20067 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and common form of non-Hodgkin’s lymphoma, characterized by marked genetic heterogeneity. The disease is difficult to treat, and patients with relapsed/refractory DLBCL often have poor outcomes. Some subsets of DLBCL have an increased reliance on B-cell receptor (BCR) activity. Spleen tyrosine kinase (SYK) is a signaling molecule essential for BCR activation. Fostamatinib, an oral SYK inhibitor, was evaluated for treatment of relapsed/refractory DLBCL in a phase 2 randomized, placebo-controlled trial1(NCT01499303), and 9 patients had clinical benefit (1 complete response, 1 partial response, and 7 stable disease). The patients with clinical benefit from fostamatinib treatment had DLBCL of germinal center B-cell (GCB) or intermediate cell of origin. We present the clinical outcomes of 2 patients from this trial who continued to benefit from fostamatinib treatment for over 6 years. Methods: Medical records for the 2 patients were retrospectively reviewed for dose regimen, clinical response, and safety data. Results: Patient A, a 63-year-old male patient with DLBCL of GCB origin, had been diagnosed with follicular lymphoma in 1996, transformation in 2002. He had undergone 1 line of treatment for follicular lymphoma and 5 treatments for DLBCL prior to fostamatinib treatment. He started fostamatinib at 100mg BID in Dec 2012, which was reduced to 100mg daily in Apr 2013, and patient continues at 100 mg QD. Patient A has maintained a complete response (CR) for > 5 years. An isolated infra-centimetric suspicious lesion was noted in Patient A in May 2019, which is stable as of January 2020 with a progressive decrease of metabolic activity. Patient B, a male with DLBCL of an intermediate cell of origin, was 69 years old at baseline with 2 DLBCL treatments prior to fostamatinib treatment since his diagnosis in Aug 2012. He started fostamatinib in May 2013 at 200 mg BID with no dose changes over the last 7 years. Patient B had a partial response (PR) per Chesson criteria since December 2014, with a sustained improved metabolic response continuing since ( > 6 years), with all but a single metastatic site no longer visible. The only serious adverse event in these 2 patients was a ventricular fibrillation and grade 4 cardiac arrest at Day 90 in Patient B, necessitating defibrillation insertion. This was deemed unrelated to treatment and resolved. Conclusions: Fostamatinib may provide durable benefit to a small subset of patients with relapsed/refractory DLBCL. 1. Flinn, I.W., et al., Eur J. Cancer 2016; 54:11-17

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

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.

DIFFUSE LARGE B-CELL LYMPHOMA SURVIVAL PROGNOSTICATION, A COMPARATIVE ANALYSIS OF CELL OF ORIGIN VS. MYC/BCL2 EXPRESSION

2019 ◽  
Vol 37 ◽  
pp. 353-353
Author(s):  
M. Rodriguez ◽  
I. Fernandez-Miranda ◽  
R. Mondejar ◽  
J. Capote ◽  
S. Rodriguez-Pinilla ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Bcl2 Expression
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