scholarly journals High-Grade B-Cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 Rearrangements Is Predominantly BCL6-Rearranged and BCL6-Expressing in Taiwan

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1620
Author(s):  
Cheng-Chih Tsai ◽  
Yung-Cheng Su ◽  
Oluwaseun Adebayo Bamodu ◽  
Bo-Jung Chen ◽  
Wen-Chiuan Tsai ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Medical Decision ◽  
High Grade ◽  
Western Countries ◽  
Medical University ◽  
Lost To Follow Up

This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover,~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

scholarly journals Real-World Outcome of Dose-Adjusted EPOCH-R, a Single-Centre Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Rachel Wong ◽  
Roopesh R. Kansara
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Time Interval ◽  
Cns Involvement ◽  
Free Survival ◽  
Aggressive B Cell Lymphoma

Introduction Dose adjusted (DA) EPOCH-R is an intensive outpatient infusional regimen, that incorporates intrathecal (IT) methotrexate to treat patients with aggressive B-cell lymphoma including HIV associated aggressive B-cell lymphoma, double-hit lymphoma (DHL), primary mediastinal B-cell lymphoma (PMBCL), Burkitt's lymphoma (BL) ineligible for intensive therapy, and gray zone lymphoma (GZL) with features in between BL and diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate non-trial, progression-free survival (PFS) and overall survival (OS) of Manitoba patients treated with DA-EPOCH-R, assess the role of prophylactic IT chemotherapy and toxicities. Methods Patients in MB approved to receive DA-EPOCH-R were identified through the CCMB Provincial Oncology Drug Program (PODP) database. Patients were included if they were older than 17 years, received at least 1 cycle of DA-EPOCH-R and with a diagnosis of HIV associated aggressive B-cell lymphoma, DHL, PMBCL, BL ineligible for more aggressive therapy, or GZL. All other diagnoses were excluded. Baseline demographic data, treatment characteristics, treatment responses, and treatment toxicity were collected. The primary endpoints of the study were progression free survival (PFS) and overall survival (OS). PFS was the time interval between the date of diagnosis to date of progression, last follow-up, or death from any cause. OS was the time interval between date of diagnosis to date of death by any cause, or last follow-up. The study was approved by the University of Manitoba Research Ethics Board and the CancerCare Manitoba Research Resource Impact Committee. Results A total of 40 patients were approved for DA-EPOCH-R between 2013 and 2019. 10 of these patients were excluded. 4 patients never received the therapy, 4 patients were treated in the relapsed setting, and 2 patients had histologies outside the inclusion criteria. Of the 30 patients included, 19 (63%) were male, 11 (37%) were female. The median age at diagnosis was 55 years (range 20-88). Our cohort was composed of DHL (n=9), triple hit lymphoma (THL, n=5), BL (n=4), GZL (n=3), and HIV-associated DLBCL (n=2). 87% (n=26) had advanced stage disease. By revised-IPI, 19 (63.3%) had poor prognosis (R-IPI ≥ 3). Response rate was 90%; CR 53.3% (n=16) and PR 37% (n=11). At a median follow-up of 25.3 months, the median PFS was 33.3 months and median OS was not reached. By histological subtype, median PFS was not reached in DHL, however THL, BL and PMBCL had worse median PFS (6.1, 8.4, and 5.6 months, respectively). Only 1 patient had CNS involvement at time of diagnosis. Of the patients with no documented CNS disease at presentation (n=29), none developed CNS involvement, including those who did not receive IT methotrexate. Median chemotherapy cycles per patient was 6 (range 1-6) and median IT treatment was 3 (range 0-6). 3 patients did not receive IT prophylaxis, and 2 stopped after 1 cycle due to intolerance. 56.7% (n=17) were able to undergo dose escalation beyond dose level 1, and 40% (n=T12) tolerated maximum dose level 3 or higher.77% of patients (n=23) experienced at least one adverse event of grade 3 or higher. 17 (57%) patients required blood transfusion at least once. 10 (33%) experienced neuropathy, 4 requiring vincristine dose reduction. 9 (30%) patients had febrile neutropenia complicating a total of 22 treatment cycles. 8 patients had grade 2-3 infectious complications. Conclusions While the real-world survival data for patients with DHL and HIV-associated lymphoma treated with DA-EPOCH-R are encouraging, those with THL, BL, and PMBCL did not attain durable response. Considering no patients (including those who did not receive IT chemotherapy) experienced CNS relapse, the role of IT chemotherapy needs to be further clarified. Disclosures No relevant conflicts of interest to declare.

BCL2 translocation in high grade B cell lymphoma (NOS, DH/TH) is associated with reduced progression free survival

2021 ◽  
pp. 1-8
Author(s):  
Sonia Gonzalez de Villambrosia ◽  
Mariana Bastos ◽  
Javier Menarguez Palanca ◽  
Jorge Gayoso Cruz ◽  
José-Tomás Navarro ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Free Survival

Survival Benefits of Patients with Non-Hodgkin’s Lymphoma Treated with Rituximab Combined with Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4625-4625
Author(s):  
Zhixiang Shen ◽  
Junmin Li ◽  
Aihua Wang ◽  
Yu Chen
Keyword(s):  
B Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Overall Response ◽  
Large B Cell

Abstract Purpose: Rituximab combined with chemotherapy has been recommended as first-line or second-line standard regimen in most subtypes of B-cell lymphoma in China by the 2004 National Comprehensive Cancer Network lymphoma therapy guideline. We have conducted a multicenter trial to evaluate the efficacy and safety of rituximab in combination with standard chemotherapy (CHOP) in patients with previously untreated or relapsed indolent and aggressive NHL. Methods: Patients received 4–8 cycles of rituximab plus CHOP every 21 days. For each cycle, rituximab (375mg/m2) was given on day 1 and CHOP started on day 3. CHOP consisted of cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2mg/dose) given intravenously on day 3, and oral prednisone 100mg on days 3–7. Results: A total of 221 patients were enrolled on the trial, 128 males and 93 females with a mean age of 49 years (range 10–83 years). The main lymphoma subtypes were small lymphocytic (15 patients, 7%), follicular (27 patients, 12%), and diffuse large B-cell (160 patients, 72%). In total, 56 patients had indolent NHL and 165 aggressive NHL. The overall response rate for all patients was 86% with 57% complete responses. In patients with indolent NHL the overall and complete response rates were 95% and 55% respectively. After a median 12 months follow up, progression-free survival in patients with indolent NHL was 88%±5% at 1 year and 83%±6% at 2 years. In the 160 patients with diffuse large B-cell lymphoma, the overall response rate was 88% with 61% complete responses, and after a mean follow-up of 6 months, predicted 1-year and 2-year progression-free survival were 88%±5% and 83%±7% respectively. Infusion-related adverse events occurred in 4% of patients, associated with the first infusion of rituximab. Subanalyses according to subtype, stage, IPI and other factors will be presented. Conclusion: Rituximab plus chemotherapy is an effective, well-tolerated treatment that achieves high response rates and long progression-free survival in both indolent and aggressive NHL.

Outcome Of Patients With Double-Hit Lymphomas Treated With CODOX-M/IVAC + R Followed By Hematopoietic Stem Cell Transplantation In British Columbia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1788-1788 ◽  
Author(s):  
Haowei (Linda) Sun ◽  
Kerry J. Savage ◽  
Aly Karsan ◽  
Graham W. Slack ◽  
Cynthia L. Toze ◽  
...  
Keyword(s):  
British Columbia ◽  
B Cell ◽  
Cell Transplantation ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Definitive Treatment ◽  
High Grade ◽  
Double Hit

Abstract Background Double-hit (DHIT) lymphoma is a heterogeneous group of non-Hodgkin lymphomas characterized by concurrent translocations involving MYC and BCL2 and typified by aggressive behavior and poor prognosis with only rare long-term survivors. There is no established treatment for DHIT lymphoma. Since 2003, the British Columbia Cancer Agency (BCCA) has adopted the use of intensive chemotherapy CODOX-M/IVAC combined with rituximab (R) followed by high-dose chemotherapy and hematopoietic cell transplantation (HSCT) as definitive treatment for DHIT lymphoma. In younger patients, an ablative matched sibling donor allotransplant (AlloSCT) is preferred over an autotransplant (AutoSCT). For all patients over the age of 60 years only AutoSCT is offered. Total Body Irradiation (TBI) is used as a part of the conditioning regimen for patients younger than 60 years of age. Here we report our provincial experience with this strategy, focusing on the ability to deliver this treatment and survival outcomes. Methods The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with non-Hodgkin lymphomas with concurrent translocation of MYC and BCL2 (DHIT lymphoma) diagnosed between January 2003-September 2012. Results 27 cases of DHIT lymphoma were identified with the following characteristics: median age at diagnosis was 55.8 years (range 35.5-70.9 years); 19 (70%) were male; 26 (96%) patients had stage 3/4 disease; 16 (59%) had bone marrow involvement. All cases were HIV negative. Histological diagnosis based on the WHO 2008 classification were: diffuse large B-cell lymphoma (DLBCL) n=8 (30%); B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCL-U) n=17 (63%); B-cell acute lymphoblastic lymphoma (ALL) n=1; high-grade B-cell lymphoma, not otherwise specified (NOS) n=1. 13 cases (48%) were transformed from an underlying indolent B-cell lymphoma (12 follicular lymphoma, 1 low-grade B-cell lymphoma NOS). CODOX-M/IVAC + R was administered in 20 patients (74%). 7 patients received alternative chemotherapy regimen (5 R-CHOP, 1 R-CVP, 1 R-ICE) due to patient and/or physician preference. 14 patients (52%) underwent HSCT (7 AutoSCT, 7 AlloSCT), including 11 patients treated CODOX-M/IVAC + R pre-transplant, and 3 patients who received other therapy. 13 patients did not undergo HSCT: primary refractory disease n=7; patient preference n=2; deconditioning n=1; age > 65 and poor performance status n=3. The clinical status at time of transplantation was CR in 5 patients (19%), PR in 8 (30%), progressive disease in 1 (4%). The conditioning regimens included: cyclophosphamide/TBI n=6, VP-16/cyclophosphamide/TBI n=4, BEAM n=3, busulfan/cyclophosphamide n=1. At last follow-up, 15 (56%) patients have died, 14 from disease progression and 1 from complications of AlloSCT. 10 (37%) patients are alive and in remission and 2 patients are alive but have relapsed. 8 of 14 HSCT recipients (6 AutoSCT, 2 AlloSCT) remain alive and free of disease compared with 2 of 13 patients who did not receive HSCT; both disease free survivors received CODOX-M/IVAC + R. Median follow-up for living patients was 31 months (range 6.5-67.3 months). 2-year EFS and OS from the diagnosis of all DHIT lymphoma patients were 35% (95% CI 16%-54%) and 45% (95% CI 20%-65%), respectively. For patients who received CODOX-M/IVAC + R, the 2-year EFS was 37%. For patients who received CODOX-M/IVAC + R followed by SCT, the 2-year EFS was 43%. Patients with BCLU/ALL/High-grade lymphoma NOS had a 2-year EFS of 27% and patients with DLBL had a 2 –year EFS of 50%. Conclusion Patients with DHIT lymphoma treated with CODOX-M/IVAC + R followed by SCT can have durable remissions. Regardless, progression during initial therapy prior to SCT remains a significant problem. Patients with DLBCL histology may have a more favorable outcome than those with BCLU. Disclosures: Savage: Eli-Lilly: Consultancy. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Sehn:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Gerrie:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Sutherland:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Villa:Roche: Honoraria, Research Funding; Lundbeck: Honoraria; Celgene: Honoraria. Song:Roche: Research Funding.

Subtypes and Treatment Outcomes of Adolescent and Adult Non-Hodgkins Lymphoma in a Resource Poor Setting

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1482-1482
Author(s):  
Yvonne Akotoa Dei-Adomakoh ◽  
Eugenia Quartey ◽  
Catherine Idara Segbefia ◽  
Elsie Amedonu ◽  
Afua Abrahams ◽  
...  
Keyword(s):  
B Cell ◽  
Treatment Outcomes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Year ◽  
High Grade ◽  
Resource Poor ◽  
Molecular Studies ◽  
Working Formulation

Abstract Introduction: Non- Hodgkins lymphomas (NHL) are a heterogeneous group of clonal malignant diseases arising from the lymphoid system with many subtypes showing both biological and clinical heterogeneity. However, the diagnosis and treatment outcomes of NHL in resource poor countries still remain a challenge in the absence of routine immunohistochemistry and molecular studies. In Ghana, a low middle-income West African country, there has been no previous systematic study of the distribution of the major subtypes of NHL. Methods: A retrospective review of case folders of all patients age 13 years and above, diagnosed with NHL between January 1, 2008 and October 31, 2013, at Korle Bu Teaching Hospital (KBTH), Accra, the largest hospital in Ghana, and one of only two hospitals in the country with a cancer unit. Information obtained from the case folders included age, sex, histological subtype, subtypes using the Working Formulation and WHO classifications. Treatment given and follow up information were also evaluated. Results: A total of 279 cases of NHL were identified within the study period. The mean overall age of the patients was 48.8 ± 17.0 years with a minimum age of 13 years and maximum 87 years. There were 156 males (55.7 %) and 123 females (43.9 %) with a male to female ratio of approximately 1.5:1. The majority of cases seen (53%) were diffuse large B-cell lymphoma. Chronic lymphocytic leukaemia/small lymphocytic lymphoma (22.2%) was the next commonest subtype. Other sub types seen, in order of frequency, included diffuse mixed cell lymphoma (6.4%), gastric lymphomas (3.9%), mediastinal B-cell lymphoma (2.9%), Burkitts lymphoma (1.8%), splenic marginal zone B-cell lymphoma (1.1%), lymphoblastic lymphoma (1.1%), mucosa-associated lymphoid tissue (MALT) type B- cell lymphoma (0.7%) and follicular lymphoma (0.7%). Others, which included anaplastic large cell lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and mycosis fungoides, collectively accounted for 3.6% of the NHL cases reviewed. Based on the Working Formulation classification with broad histologic categories of low-, intermediate-, and high-grade lymphomas, 83 out of 279 (29.7%) had low grade NHL, 170 (60.7%) intermediate and 26(9.4%) had aggressive/high grade NHL. Table 1 shows chemotherapy regimens administered and first year treatment outcomes. One-year survival for cases of NHL in the study was found to be high (98.6%). However, only 115/279(41.2%) of patients were seen for follow up in the second year post-treatment, with 85 of these (73.9%) still in clinical remission. In the third year only 37/279(13.3%) reported for follow up. Conclusions: This study provides a baseline overview of the distribution of NHL subtypes and their outcomes in adolescent and adult patients in a resource constrained setting. Patient loss to follow up in the 2nd and 3rd year post treatment was very high and the reasons for this should be explored in a future study. Immunohistochemistry, cytogenetics and specific molecular studies, which are important in characterization of NHL, should be made affordable and accessible in low-income countries. Table 1. FIRST YEAR OUTCOME FOR ALL NHL SUBTYPES AND TREATMENT GIVEN TYPE OF CHEMOTHERAPY GIVEN CHOP CVP R-CHOP CHLORAMBUCIL + PREDNISOLONE CODOX-M/ IVAC TOTAL INDOLENT TYPE NHL CR 37 34 2 2 0 75 (26.9%) PR 3 1 0 0 0 4 (1.4%) NR 1 0 0 0 0 1 (0.4%) LTF 2 0 0 0 0 2 (0.7%) TOTAL 43 (15.5%) 35 (12.5%) 2 (0.7%) 2 (0.7%) 0 (0.0%) 82(29.4%) INTERMEDIATE TYPE NHL CR 120 3 9 0 0 132 (47.3%) PR 32 4 0 0 0 36 (12.9%) NR 1 0 0 0 0 1 (0.4%) LTF 2 0 0 0 0 2 (0.7%) TOTAL 155 (55.6%) 7 (2.5%) 9 (3.2%) 0 (0.0%) 0 (0.0%) 171 (61.3%) AGGRESSIVE TYPE NHL CR 9 0 3 0 1 13 (4.65%) PR 12 0 0 0 1 13 (4.65%) NR 0 0 0 0 0 0 (0.0%) LTF 0 0 0 0 0 0 (0.0%) TOTAL 21 (7.5%) 0 (0.0%) 3 (1.1%) 0 (0.0%) 2 (0.7%) 26 (9.3%) GRAND TOTAL 219 (78.5%) 42 (15.1%) 14 (5.0%) 2 (0.7%) 2 (0.7%) 279 (100%) CR: CLINICAL REMISSION, PR: POOR RESPONSE, NR: NO RESPONSE, LTF: LOST TO FOLLOW-UP Disclosures No relevant conflicts of interest to declare.

scholarly journals Survival and Risk of Central Nervous System Recurrence in Burkitt or High-Grade B-Cell Lymphoma in the DA-EPOCH-R Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2983-2983
Author(s):  
Dominic Decker ◽  
Pamela C Egan ◽  
Diana O Treaba ◽  
Adam J Olszewski
Keyword(s):  
B Cell ◽  
High Intensity ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Cns Involvement ◽  
Cns Prophylaxis ◽  
Cns Relapse

Abstract Background: The 2017 World Health Organization (WHO) classification distinguished new categories of high-grade B-cell lymphoma (HGBCL). Treatment of these lymphomas is in flux, as some were historically classified as DLBCL and treated with the RCHOP regimen, while others, akin to Burkitt lymphoma (BL), were treated using high-intensity regimens (e.g. CODOX-M/IVAC or hyper-CVAD) that include systemic high-dose methotrexate (HDMTX) as central nervous system (CNS) prophylaxis . Recently, the less intensive DA-EPOCH-R regimen has been increasingly applied for BL or HGBCL with concurrent MYC and BCL2 and/or BCL6 rearrangements based on phase 2 data (Dunleavy et al., NEJM 2013). We examined progression-free survival (PFS) and risk of CNS relapse among HGBCL/BL patients treated in our institution. Methods: In this retrospective series from an academic center, we integrated cancer registry and electronic medical records for all patients treated for BL or HGBCL at Lifespan Cancer Institute in 2005-2017. We designated as "HGBCL" all cases with concurrent MYC and BCL2/BCL6 rearrangements, or those previously diagnosed as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (per WHO 2008). We compared characteristics of patients treated with intensive regimens or with DA-EPOCH-R, as well as their PFS (using log-rank test) and cumulative incidence function (CIF) of CNS relapse (using Gray's test). Results: Among 64 patients with BL (n=38) and HGBCL (n=26), those with BL were somewhat younger (median age 52 versus [vs.] 61 years), more often male (84% vs. 58%), HIV-positive (29% vs. 8%), or with CNS involvement at baseline (21% vs. 4%). Among HGBCLs, 58% had a MYC rearrangement, whereas 31% had concurrent MYC and BCL2/BCL6 rearrangements. Eight patients who did not receive chemotherapy (median age, 78 years) were excluded from outcome analysis. Compared with patients with BL, those with HGBCL more often received DA-EPOCH-R (41% vs. 15%) or R-CHOP (27% vs. 12%), and less often high-intensity regimens (32% vs. 73%, P=.027). Compared with patients treated using high-intensity regimens, those treated with DA-EPOCH-R were significantly older (61 vs. 49 years, P=.023), with high/high-intermediate International Prognostic Index (IPI, 86% vs. 50%, P=.027), or diagnosis after 2010 (86% vs. 53%, P=.049). There was no difference in baseline CNS involvement (P=.68) or receipt of intrathecal prophylaxis (P=.16) between DA-EPOCH-R and high-intensity regimens. After median follow-up of 5.7 years, we observed 12 recurrences, including 5 (42%) in the CNS. Median PFS was not reached, whereas 3-year PFS was 56% (95% confidence interval [CI], 42-68%), numerically better in BL than in HGBCL (63% vs. 45%, P=.33, Fig. A). Overall survival at 3 years was also 56% (95%CI, 41-68%). Factors associated with shorter PFS included age >60 years (log-rank P=.017), poor performance status (P<.001), high/high-intermediate IPI (P=.0003), and lack of CNS prophylaxis (P=.021). Treatment with DA-EPOCH-R rather than a high-intensity regimen was also associated with worse PFS (P=.001), but not when stratified by histology and age (P=.14). HIV status (P=.53) or CNS involvement at baseline (P=.15) were not prognostic. Survival after recurrence was dismal (median, 1 month, 95%CI, 0.2-3.4), despite 58% of patients receiving salvage therapy. The 3-year CIF of CNS recurrence was 9% (95%CI, 3-18%), and higher in patients with CNS involvement at baseline (P=.002). All CNS recurrences occurred during the first year of follow-up and were among patients receiving DA-EPOCH-R (35.7% vs. 0% for other regimens, P=.0004). Administration of HDMTX for CNS prophylaxis was associated with a numerically lower risk of CNS recurrence (3% vs. 16% without, P=.09, Fig. B). Conversely, we observed no difference in CNS relapse with or without intrathecal prophylaxis (9% vs. 8%, P=.84, Fig. C). Conclusions: The high proportion of CNS recurrences despite prophylaxis, and very poor outcomes at relapse, indicate persistent major areas of need in BL/HGBCL. Outcomes of DA-EPOCH-R were heavily influenced by selection bias (as evidenced by unfavorable characteristics of patients selected for this regimen), so evaluation of this regimen in comparison with high-intensity approaches is warranted in a larger sample. However, our data suggest that in BL/HGBCL systemic HDMTX may be essential for effective CNS prophylaxis. Disclosures Olszewski: TG Therapeutics: Research Funding; Genentech: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding.

Patients with "Single-Hit" but Not MYC -Amplified Non-Burkitt High-Grade B Cell Non-Hodgkin Lymphomas Experience Poor Survival Outcomes and May Benefit from Intensive Induction Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2696-2696
Author(s):  
Daniel J. Landsburg ◽  
Marissa K. Falkiewicz ◽  
Jennifer J.D. Morrissette ◽  
April M. Schrank-Hacker ◽  
Sunita Dwivedy Nasta ◽  
...  
Keyword(s):  
B Cell ◽  
Induction Therapy ◽  
Research Funding ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Baseline Characteristics ◽  
Ecog Ps

Abstract Introduction While patients (pts) with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma (BCLU) harboring rearrangement of MYC (MYC-R) face a poor prognosis as compared to DLBCL/BCLU pts without MYC-R, the prognosis of DLBCL/BLCU pts with MYC-R in the absence of rearrangements of BCL2 (BCL2-R) and BCL6 (BCL6-R) has not clearly been reported in the literature. Additionally, it is not well known whether amplification of MYC in the absence of MYC-R portends a poor prognosis for DLBCL/BCLU pts. Here, we analyze outcomes for these pts in comparison to DLBCL/BCLU pts without MYC-R or MYC amplification. Methods Pts diagnosed with DLBCL or BCLU treated at the University of Pennsylvania and Northwestern University from 3/2002-3/2015 whose diagnostic specimens underwent fluorescence in situ hybridization for MYC-R with8q24 breakapart and/or t(8;14)(q24;q32) fusion probes were included in this analysis. Pts with primary CNS and HIV-associated lymphoma were excluded. Cases with MYC-R but not BCL2-R and BCL6- R were defined as single hit (SH), cases with MYC-R as well as BCL2 -Rand/or BCL6-R as double hit (DH), cases with >4 copies of MYC as amplified (MYC amp) and cases without MYC-R and ≤4 copies of MYC as normal (MYC normal). Therapy was given at the discretion of the treating clinician. Progression free survival (PFS) was defined as time from diagnosis to radiographic progression, regimen change, death or last follow-up. Overall survival (OS) was defined as time from diagnosis to death or last follow-up. Data were censored on 7/1/15. Results 224 pts were included in the full analysis: 190 MYC normal, 19 SH and 15 MYC amp. An additional 46 DH pts were analyzed for PFS and OS only. No pts were both SH and MYC amp. Pts baseline characteristics were reported as follows: 52% female, 47% age >60 years (yrs), 66% LDH >normal, 62% stage ≥3, 15% lymphomatous involvement of bone marrow, 11% ECOG performance status (PS) >2, 66% extranodal disease, 29% B symptoms, 42% International Prognostic Index (IPI) score ≥3, 4% BCLU histology and 18% low-grade transformation. Only the presence of BCLU histology differed significantly between SH and MYC normal pts (26% vs. 1%, p=0.001) and between MYC amp and MYC normal pts (13% vs. 1%, p=0.028). PFS and OS are depicted in Figure 1. For all pts, the median length of follow-up was 15.4 months (mos) (range 0.1-156.1 mos), median PFS not yet reached and median OS not yet reached. Rates of PFS and OS at 2 yrs for MYC normal, SH and MYC amp pts were 72%, 52%, 62% and 81%, 65%, 74%, respectively. When compared to MYC normal pts, SH pts experienced significantly shorter rates of PFS (p=0.043) and OS (p=0.038) at 2 yrs; however, rates of PFS and OS at 2 yrs did not differ significantly between MYC amp and MYC normal pts (p=0.29 and p=0.67, respectively). For comparison, rates of PFS and OS at 2 yrs for DH pts were 32% and 37%, and did not differ significantly from those of SH pts (p=0.26 and p=0.18, respectively). For SH patients, rates of PFS and OS at 2 yrs for those receiving induction therapy with R-CHOP vs. intensive induction (II), defined as either R-EPOCH, R-hyperCVAD or R-CODOX-M/IVAC, were 25% vs. 76% (p=0.13) and 75% vs. 73% (p=0.94), respectively. Baseline characteristics significantly associated with progression on univariate analysis (UVA) were LDH > normal (HR 2.50, 95% CI 1.20-5.17, p=0.014), ECOG PS >2 (HR 2.17, 95% CI 1.05-4.70, p=0.036) and B symptoms (HR 2.49, 95% CI 1.48-4.19, p=0.001); however, only B symptoms remained statistically significant on multivariate analysis (MVA) (HR 2.66, 95% CI 1.41-5.01, p=0.003). Baseline characteristics significantly associated with death on UVA were LDH > normal (HR 3.99, 95% CI 1.19-13.4, p=0.025), ECOG PS >2 (HR 3.19, 95% CI 1.29-7.90, p=0.012), B symptoms (HR 2.70, 95% CI 1.31-5.57, p=0.007) and SH vs. MYC normal (HR 2.59, 95% CI 1.06-6.31, p=0.037); however, no factor remained statistically significant on MVA. Conclusions This analysis of the largest reported series of SH and MYC amp pts suggests inferior rates of PFS and OS at 2 yrs for SH pts, but not MYC amp pts, as compared to MYC normal pts. SH pts receiving II experienced similar rates of PFS and OS at 2 yrs as compared to MYC normal pts. Much like DH pts, SH pts should be considered a poor prognosis subgroup of non-Burkitt high-grade B cell non-Hodgkin lymphomas and identified as candidates for risk-adapted and/or targeted therapies. Figure 1. Figure 1. Disclosures Dwivedy Nasta: Millenium Takeda: Research Funding; BMS: Research Funding. Svoboda:Immunomedics: Research Funding; Celldex: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding. Schuster:Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Hoffman-LaRoche: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Novartis: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees. Mato:Gilead: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding. Petrich:Seattle Genetics: Consultancy, Honoraria, Research Funding.

Prevalence and Clinico-Pathological Attributes of c-MYC Rearranged High-Grade B-Cell Non Hodgkin Lymphomas (NHL): Single Centre Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5031-5031
Author(s):  
Manju Sengar ◽  
Sridhar Epari ◽  
Hasmukh Jain ◽  
Tanuja Shet ◽  
Sumeet Gujral ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
High Grade ◽  
Ki 67 ◽  
Large B Cell ◽  
Who 2008

Abstract Introduction: MYC rearrangement in high-grade B-cell NHL(non-burkitt), either as single hit or double hit, has significant prognostic and therapeutic implications. There is remarkable paucity of data on frequency and clinico-pathological features of MYC-rearranged large B-cell lymphomas from developing world. Method: This study included de-novo high grade B-cell NHL cases (>15 years of age) registered at Tata Memorial Centre between January 2013- December 2014. Demography details, clinical features (stage at presentation, bone marrow involvement, presence and extent of extranodal involvement, B-symptoms, international prognostic index),original histopathological diagnosis, chemotherapy and radiotherapy details were recorded from electronic medical or paper case records. Response to therapy, relapses or death if any, status at last follow up, dates of relapse and/or death and last follow up were recorded. All cases were reviewed by expert hematopathologists to categorize the high grade B-cell NHL as per the WHO-2008 classification of hematopoietic malignancies. All cases with adequate formalin-fixed paraffin embedded (FFPE) blocks were evaluated by FISH for c-MYC , BCl-2 and BCl-6 using Vysis dual colour break apart probes. Cases which showed >10% cells with split signal were considered to harbor rearrangement. Result: A total of 114 cases of de-novo high-grade B-cell NHL with adequate FFPE blocks were evaluated. Based on WHO 2008 classification, 112 cases were classified as diffuse large B-cell lymphoma (DLBL)) and 1 each as Burkitt's (BL) and B- cell lymphoma unclassifiable -intermediate between DLBL and BL(BCLU). A total of 9/112 (8%) cases of DLBL showed MYC rearrangement. One of these 9 cases had both MYC and BCl-2 rearrangement. BCLU did not demonstrate MYC or BCl-2 rearrangement. The Ki-67 index was variable (40-95%)in MYC rearranged cases. The median age of the c-MYC rearranged cases was 55 year (range-23-79 years). 88% were males. Advanced stage disease, bulky mass and extranodal disease was seen in 67%, 44% and 55% of cases respectively. All but one patient had high LDH, however none of the patients had elevation more than 2XULN. These patients received rituximab based chemoimmunotherapy (RCHOP-4,RCEOP-4, REPOCH-1) and 77% achieved complete response. At median follow up of 5 months, 1 year-overall survival and progression free survivals were 80% and 75% respectively. There were no significant differences in clinical features (except higher proportion of males in the c-MYC rearranged subset), LDH levels, ki-67 index , response to therapy and survival between DLBL with or without c-MYC rearrangement Conclusion: In our study 8% of all DLBL cases showed c-MYC rearrangement. The frequency of double hit lymphoma was less than 1% (0.8%). Disclosures No relevant conflicts of interest to declare.

Prospective Management of Primary Testicular Lymphoma (PTL) with Doxorubicin-Based Chemotherapy, Prophylactic Intrathecal (IT) Methotrexate and Radiotherapy (RT), but without Rituximab: Results from IELSG.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2454-2454 ◽  
Author(s):  
Andreas H. Sarris ◽  
Umberto Vitolo ◽  
Emanuele Zucca ◽  
George Z. Rassidakis ◽  
Jeffrey Medeiros ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Contralateral Testis ◽  
Large B Cell Lymphoma ◽  
Frequent Relapses ◽  
Large B Cell

Abstract Introduction: PTL is a rare extranodal lymphoma characterized by a continuous pattern of systemic relapses in spite of doxorubicin-based therapy. There are also frequent relapses in the contralateral testis and the central nervous system (CNS). Therefore we decided to determine whether prophylaxis of the CNS and the contralateral testis would modify the pattern of relapse of PTL. Patients and methods: From 1993 to February 2002 in IELSG member institutions patients with PTL (presenting with testicular enlargement) were managed with doxorubicin-based therapy according to institutional policy, with the addition of four doses of IT methotrexate (15 mg) during the first 6 weeks. At the end of chemotherapy scrotal RT (30 Gy) was given to all patients and 30–36 Gy nodal RT to those with stage II disease. Rituximab was not used in this cohort because it was not yet generally available for patients with diffuse large B-cell lymphoma. Results: There were twenty seven patients; two refused chemotherapy and/or RT/IT therapy and one RT, leaving 24 eligible for analysis. Median age was 60 years (range 31–80). Ann Arbor stage was I in 17, II in four, and four in three patients. B-symptoms were present in one patient. The right testis was involved in 13 and the left in 11 patients. Serum LDH was elevated in four of 21 with available values. No patient had CNS involvement at diagnosis. Pathology was diffuse large B-cell lymphoma in all patients. Treatment was CHOP in 21, alternating triple therapy in two, and hyper-CVAD in one patient. Three patients died during therapy: one from neutropenic sepsis and two from toxicity of systemic methotrexate. The remaining 21 patients achieved a complete remission. With a median follow-up of 57 months (range 8–123) for survivors, seven patients have relapsed, three in the CNS. There were no testicular relapses. Eight patients have died: three from toxicity during induction, three from relapsed lymphoma, one from gastric carcinoma and one from sudden death, both in complete remission. At 5 years the projected progression-free survival was 78%, and survival 66%, but both without an apparent plateau. Freedom from progression in the CNS was 84%, with a plateau. Conclusions: Patients with PTL treated prospectively with doxorubicin-based therapy before the availability of rituximab exhibit the continuous pattern of relapse previously reported. Scrotal RT seems eliminate testicular relapses, and prophylactic IT methotrexate seems to reduce, but not eliminated CNS relapses. These need to be confirmed by longer follow-up. The ongoing IELSG-10 should determine whether the addition of rituximab alters the continuous pattern of systemic relapses. Future studies should determine the molecular basis of the continuous relapses and minimize both systemic and CNS relapses.

Comparison Between R-CHOP Vs R-CHOP Plus Etoposide in Untreated Patients with Primary Mediastinal B-Cell Lymphoma: Preliminary Findings

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5437-5437
Author(s):  
Felipe Vieira Rodrigues Maciel ◽  
Roberta Shcolnik Szor ◽  
Debora Levy ◽  
Rodrigo Santucci ◽  
Juliana Pereira
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Mediastinal Mass ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Significant Difference ◽  
Overal Survival

Abstract Background: Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma originating from the thymus with its own epidemiological, clinical, immunophenotypic and prognostic features and that was included as a distinct clinical entity in the last World Health Organization classification (2008). It is more prevalent in young female, and is characterized by a large mediastinal mass, with frequent infiltration of adjacent structures. Dissemination by distant sites may be identified at diagnosis or during the disease progression. It shows many similar aspects to nodular sclerosis Hodgkin’s Lymphoma in terms of clinical, pathological and immunohistochemical features. The standard treatment is based on multidrug regimens containing anthracyclines associated with rituximab and consolidation with radiotherapy. A recent study published in the NEJM in 2013, with a single-arm treatment with infusional dose-adjusted DA-EPOCH-R with no radiotherapy in untreated PMBCL, demonstrated 97% of overall survival (OS) and 93% of event-free survival (EFS) with a median of 5 years of follow-up. Methods: We analyzed retrospectively 40 patients with PMBCL treated at São Paulo’s Cancer Institute from June 2007 to January 2014. The objectives of the study were to compare the complete response (CR), progression-free survival (PFS) and overall survival (OS) rates between two different treatment strategies. All patients were initially evaluated with blood tests, whole-body computed tomography (CT) or fluorodeoxyglucose-positron-emission tomography (PET-CT) and bone marrow biopsy. Two chemotherapy regimens were used in the patient’s treatment: 6 to 8 cycles of conventional R-CHOP 21 with or without radiation therapy (n = 23) and R-CHOP regimen with addition etoposide (DA-EPOCH-R or R-CHOEP) with or without radiotherapy (n = 17). After 4 cycles of treatment, patients were evaluated for response to determine the total number of cycles (6 or 8). Results Among the 40 enrolled patients, 65% were female with median age of 31 years (range 14 to 62 years). The median size of the mediastinal mass was 13cm in the longest axis. Half of the patients (50%) were in advanced stage (III or IV of Ann Arbor staging) and 75% were in good prognosis category of R-IPI ( 1 or 2 risk factors of the International Prognostic Index Score for non Hodgkin lymphoma). 57,5% of patients were treated with R-CHOP and 42,5% had etoposide as part of the their treatment regimen (12,5% DA-EPOCH-R and 30% R-CHOP plus etoposide (100mg/m2 D1-D3). There was no statistically significant difference in CR rate between RCHOP vs RCHOP + etoposide (86.9% vs 86.6%). There were no differences in PFS or OS for the 2 groups (p=0.8202 and 0.9410). Conclusion The addition of etoposide to RCHOP regimen appears to increase OS and PFS of patients with untreated PMBCL as previously demonstrated. In our service, where there is difficult in hospitalization for the administration of infusional regimens such as DA-EPOCH-R, it was necessary to adjust for outpatient to R-CHOEP. The comparison between the two groups (RCHOP vs RCHOEP/DA-EPOCH-R) showed no statistically significant difference in CR, OS and PFS. However, the median of follow-up of patients who received etoposide was not sufficient to analyze the data adequately. Overall Survival Figure 1. Overal survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.8202) Figure 1. Overal survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.8202) Progression Free Survival Figure 2. Progression free survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.9410). Figure 2. Progression free survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.9410). Disclosures No relevant conflicts of interest to declare.

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