Primary Refractory Double Hit Diffuse Large B Cell Lymphoma: Complete Response with Ibrutinib and Rituximab

2018 ◽  
Vol 18 ◽  
pp. S294 ◽  
Author(s):  
Arnav Sethi ◽  
G. Obi ◽  
A. Manhas ◽  
A. Scholoff ◽  
N. Vu ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

scholarly journals Differential Outcomes of Synchronous and Metachronous Diffuse Large B-Cell Lymphoma Transformed from Follicular Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5409-5409
Author(s):  
Natalie Pei Xin Chan ◽  
Ryan Mao Heng Lim ◽  
Lay Poh Khoo ◽  
Chee Leong Cheng ◽  
Leonard Kwan Cheong Tan ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Pathological Characteristics ◽  
Large B Cell Lymphoma ◽  
Response To Chemotherapy ◽  
Double Hit ◽  
Large B Cell

Abstract Aim: Composite histologies of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) may be present synchronously at diagnosis or metachronously at the time of transformation of a formerly diagnosed FL. The aim of this study was to examine their clinico-pathological characteristics and treatment outcomes. Method: Patients who were consecutively diagnosed with composite FL/DLBCL (n=120) and FL (n=346) from 2001-2017 at the National Cancer Centre Singapore were retrospectively analyzed. Chi-squared tests and multivariate logistic regression were performed to evaluate clinico-pathological associations between the two cohorts. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: Amongst the FL cases, 21 patients (6.1%) with metachronous transformed FL/DLBCL were identified. The median lag time from diagnosis of FL to DLBCL transformation was 47 months (range, 7.8-168). Clinico-pathological features in synchronous and metachronous FL/DLBCL were similar, with both entities demonstrating a male preponderance (67% male and 33% female). Median age at diagnosis was 67 years (range, 41-81) and 60 years (range, 24-90) for metachronous and synchronous FL/DLBCL, respectively. The cell-of-origin by Han's criteria was similar (metachronous: GCB 52%, ABC 43%, unknown 5%; synchronous: GCB 38%, ABC 57%, unknown 5%; p = 0.21), as were the occurrence of C-MYC/BCL2/BCL6 double-hit rearrangements. However, survival from the time of DLBCL development was significantly worse (median, 3 vs 12 years) for metachronous compared to synchronous FL/DLBCL (HR 2.20, 95%CI 0.88-5.49, p = 0.022). Double-hit, advanced stage, and use of non-RCHOP regimens (OR 7.54, 95%CI 2.84-20.1, p = 0.0001) were associated with lack of complete response to chemotherapy. In metachronous FL/DLBCL, the R-CHOP regimen was less commonly used (77% vs 56%, p = 0.049). Correspondingly, complete response to chemotherapy was less likely in metachronous cases (38% vs 63%, p = 0.037). Conclusion: Metachronous and synchronous FL/DLBCL share similar clinico-pathological characteristics. A preceding diagnosis of FL however, predicts for significantly worse survival outcomes and suboptimal responses to chemotherapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals How I treat double-hit lymphoma

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 590-596 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Involvement ◽  
B Cell Lymphoma ◽  
World Health ◽  
Large B Cell Lymphoma ◽  
Double Hit Lymphoma ◽  
Increased Risk ◽  
Double Hit ◽  
Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

scholarly journals Large B-Cell Lymphoma with T-Cell–Rich Background and Nodules Lacking Follicular Dendritic Cell Meshworks: A Case Report with Complete Response to Chemotherapy and a Review of the Literature

2020 ◽  
Vol 5 (11) ◽  
pp. 561-565
Author(s):  
Walid Shalata ◽  
Ismaell Massalha ◽  
Kayed Al-Athamen
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Follicular Dendritic Cell ◽  
Large B Cell Lymphoma ◽  
Follicular Dendritic ◽  
Large B Cell

In this report, we describe a 38-year-old male with a very rare type of lymphoma, large B cell lymphoma with T cell-rich background and nodules lacking follicular dendritic cell meshworks (THRLBCL). In 2016 the patient presented hot flashes and night sweats (B-symptoms) and peripheral edema. He was treated with R-CHOP (doxorubicin, vincristine, cyclophosphamide, rituximab and Prednisone) chemotherapy, a Positron emission tomography–computed tomography (PET-CT) scan was performed after four cycles of treatment which showed radiologic complete response and blood test (complete blood count (CBC)) results showed normal ranges. As of September, 2020 he patient remains in complete remission. We searched the literature for descriptions of cases spanning the diagnostic spectrum of THRLBCL and we identified only five cases worldwide. The last reported case was in 2014 with distinctive features that were difficult to classify according to the World Health Organization criteria or previously described variants. Our patient is the sixth case of THRLBCL to be reported. He is the youngest of the reported cases and the first from Israel and the Middle East.

scholarly journals Evolution of frontline treatment of diffuse large B-cell lymphoma: a brief review and recent update

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1933 ◽  
Author(s):  
Jung Yong Hong ◽  
Cheolwon Suh ◽  
Won Seog Kim
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Targeted Agents ◽  
Cell Of Origin ◽  
Cell Subtype ◽  
Large B Cell Lymphoma ◽  
Frontline Treatment ◽  
Double Hit ◽  
Large B Cell

Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL.

Survival outcomes of diffuse large B-cell lymphoma by association with concurrent or antecedent follicular lymphoma and double hit status

2019 ◽  
Vol 60 (13) ◽  
pp. 3266-3271
Author(s):  
Amir Behdad ◽  
Craig S. Boddy ◽  
Angela J. Fought ◽  
Timothy Taxter ◽  
Marissa K. Falkiewicz ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

PD‐L1 expression is low in large B‐cell lymphoma with MYC or double‐hit translocation

2019 ◽  
Vol 37 (4) ◽  
pp. 375-382 ◽  
Author(s):  
Mette Vestergaard Elbæk ◽  
Mette Ølgod Pedersen ◽  
Marie Fredslund Breinholt ◽  
Anupama Reddy ◽  
Cassandra Love ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

Clinical Outcome and Survival of EBV-Positive Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5005-5005
Author(s):  
Brady Beltran ◽  
Pilar Quinones ◽  
Domingo Morales ◽  
Alex Capellino ◽  
Roberto Miranda ◽  
...  
Keyword(s):  
Risk Factors ◽  
B Cell ◽  
Median Survival ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Large B Cell

Abstract Abstract 5005 Background EBV-positive diffuse large B-cell lymphoma (DLBCL) is a new entity included provisionally in the most recent WHO Classification of lymphoid neoplasms. It usually affects elderly patients and has a poor survival. The goal of this study was to evaluate clinical characteristics and survival of EBV-positive DLBCL. Methods Between January 2002 and June 2008, twenty patients with EBV-positive DLBCL were deemed eligible for the study. Of those, eighteen cases were evaluable. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or Pax-5 expression by immunohistochemistry (IHC). Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of bcl-6, CD10, CD30 and MUM-1 by IHC. The survival estimates were calculated using the Kaplan-Meier method and the log-rank test was used to compare the survival curves. Results The mean age was 72.7 years (range 34-95 years). B symptoms occurred in 6 patients (33%). Four patients (22%) presented with stage I, 4 (22%) with stage II, 5 (28%) with stage III and five (28%) with stage IV. The IPI risk score was low in 6 patients (33%), low intermediate in 2 (11%), high intermediate in 6 (33%) and high in 4 (22%). Extranodal disease occurred in 10 patients (55%); the most common extranodal sites were gastrointestinal tract (n=5), lung (n=3), suprarenal gland (n=1), bone (n=1), skin (n=1), tonsils (n=1) and bone marrow (n=1). Of 13 evaluated cases, eleven cases (83%) were of non-germinal center and 2 cases (17%) were of germinal center subtype. According to the Oyama score, 3 cases (17%) had 0 risk factors, 11 patients (61%) had 1 risk factor and 4 (22%) had 2 risk factors with median survival of 41, 11 and 1.5 months, respectively. Eight patients (44%) did not receive chemotherapy because they had a poor performance status. Ten patients (56%) received chemotherapy, eight received CHOP and two received R-CHOP. Overall response was 70% with a complete response in 7 cases and progressive disease in 3. No patients exhibited a partial response. Median survival for the entire group was 10 months; the median survival for the treated group was 17 months while for the untreated group was 2.5 months. The 2 patients treated with R-CHOP obtained a complete response. Conclusions EBV-positive DLBCL is an aggressive entity with frequent extranodal disease and a poor prognosis. The latter appears to be due to high IPI scores, non-germinal center immunophenotype and/or the presence of EBV. Although, EBV-positive DLBCL seems to respond well to R-CHOP, the survival remains dismal. Prospective studies are needed to validate EBV's prognostic, predictive and therapeutic value in DLBCL in the post-rituximab era. Disclosures No relevant conflicts of interest to declare.

MYC Translocation Partner Gene Determines Survival in Large B-Cell Lymphoma with MYC- or Double Hit MYC/BCL2 Translocation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 542-542
Author(s):  
Mette Ølgod Pedersen ◽  
Anne Ortved Gang ◽  
Tim Svenstrup Poulsen ◽  
Helle Knudsen ◽  
Anne M Falensteen Lauritzen ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Prospective Cohort ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Partner Gene ◽  
Double Hit ◽  
Split Signal ◽  
Large B Cell

Abstract Abstract 542 MØP and AOG shared the first authorship. Background: In large B-cell lymphoma (LBCL) chromosomal translocations involving the MYC protooncogene (8q24) with or without concurrent BCL2 translocation (double hit) have been associated with inferior survival. We recently found in a prospective cohort of LBCL patients that double hit MYC/BCL2 translocations had no impact on overall survival (Pedersen et al., Eur.J.Haematol. 2012). However, further stratification of patients with double hit MYC/BCL2 translocation indicated an inferior survival related to immunoglobulin MYC translocation partner gene (MYC-IG). We sought to confirm this in a larger prospective cohort of LBCL patients. Materials and methods: All patients diagnosed with LBCL (diffuse large B-cell lymphoma, DLBCL, or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, BCLU), at Dept. of Pathology and subsequently treated at Dept. of Hematology, Copenhagen University Hospital in Herlev, were prospectively collected from 2009–2011. Tumors were classified according to morphology and immunophenotype (2008 WHO classification). Chromosomal translocations were examined with FISH, including BCL2, MYC, MYC/IGH, kappa and lambda probes. Cases which were MYC/IGH fusion signal positive or MYC split signal positive + kappa or lambda split signal positive were classified as MYC-IG. Clinical data were collected from patient files. A total of 237 patients (163 primary LBCL, 49 transformed LBCL, 25 relapsed LBCL) were included. Results: MYC translocation was found in 28/225 patients, with translocation partner gene MYC-IG in 12/24 patients and MYC-nonIG in 12/24 patients. Double hit MYC/BCL2 was found in 23/228 patients, with translocation parter gene MYC-IG in 9/19 patients and MYC-nonIG in 10/19 patients. Cox regression models were performed for calculating p-values and survival curves (Fig. 1+2). The presence of MYC translocation or MYC/BCL2 double hit translocation showed no correlation with survival. However, stratification according to MYC translocation partner gene showed an inferior overall survival related to MYC-IG compared to MYC-nonIG (p=0.03), and to MYC translocation negative (Fig. 1). Among patients with double hit MYC/BCL2 translocation, a similar picture evolved where MYC-IG/BCL2 had an inferior overall survival compared to MYC-nonIG/BCL2 (p=0.006) and MYC/BCL2 translocation negative cases (Fig. 2). Most patients were treated with standard Rituximab containing chemotherapy and treatment was comparable between the groups. Conclusion: MYC translocation, with or without concurrent BCL2 translocation, was associated with inferior survival only if MYC had immunoglobulin translocation partner gene, in this prospective cohort of LBCL patients. This suggests that prognostic stratification by MYC and MYC/BCL2 translocations should include examination of MYC translocation partner genes. An overrepresentation of transformed cases which was observed in the MYC-nonIG group could lead to an underestimation of the prognostic effect of MYC-IG. Disclosures: No relevant conflicts of interest to declare.

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