R-CHOP in Primary Mediastinal B-Cell Lymphoma (PMBL): Results from the UK NCRI R-CHOP 14 v 21 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2689-2689
Author(s):  
Mary Gleeson ◽  
Eliza A Hawkes ◽  
David Cunningham ◽  
Nick Chadwick ◽  
Nick Counsell ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Mediastinal Mass ◽  
Cell Lymphoma ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Who 2008

Abstract Introduction: Primary Mediastinal B-cell Lymphoma (PMBL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) comprising approximately 10% of cases. Studies in the pre-rituximab (R) era suggested a benefit for dose intensified regimens such as V/MACOP-B over cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). However no prospective studies comparing dose intensified regimens with R-CHOP have been performed in the rituximab era and controversy exists regarding the current optimal induction chemotherapy. R-CHOP +/- involved field radiotherapy (IFRT) is the most commonly used regimen worldwide with reported 5-yr relapse free and overall survival rates of 68-81% and 79-91% respectively; but with the exception of the MInT trial (which evaluated young patients with PMBL aged ≤60 years with an age-adjusted International Prognostic Index of 0-1), the evidence for R-CHOP in PMBL comes from retrospective studies. The aim of this analysis was to evaluate the outcomes for R-CHOP treated PMBL patients within the UK NCRI R-CHOP 14 v 21 prospective trial. Methods: The phase III randomised UK R-CHOP-14 vs 21 trial assessed R-CHOP given 2 weekly versus 3 weekly in 1080 DLBCL patients aged ≥ 18years who were enrolled from 2005-2008. We previously reported that R-CHOP-14 was not superior to R-CHOP-21 for overall survival (OS), progression free survival (PFS), response rate or safety (Cunningham D et al, Lancet May 2013). Patients with PMBL were not excluded from participation and we identified cases by searching the trial database for patients with a mediastinal mass (≥5cm) who also fulfilled the WHO 2008 clinical criteria for sites of involvement (absence of disease involvement outside of the thorax +/- cervical / supraclavicular lymph node involvement). Response was assessed according to the IWG 1999 criteria. PFS and OS were calculated from date of randomisation and analysed using Kaplan-Meier methods. Results: 50/1,080 (4.6%) patients from the R-CHOP 14 v 21 study database met the WHO 2008 criteria for PMBL and were included in this analysis, with a median follow-up of 7.3 years. The median age at diagnosis was 38.5 years (range 22-78 years). 50% (n=25) of the patients were female. All patients had stage I (n=18, 36%) or II (n=32, 64%) disease. The median mediastinal mass diameter was 11.1cm (range 6-23cm) and 70% (n=35) of patients had a mediastinal mass ≥10cm. 28 (56%) and 22 (44%) patients were treated with R-CHOP-21 and R-CHOP-14 respectively. On completion of R-CHOP chemotherapy CT response was complete (CR) in 43% (n=21), partial (PR) in 49% (n=24), stable disease (SD) in 2% (n=1) and progressive disease (PD) in 6% (n=3), one patient was non-evaluable. IFRT was administered to 58% of patients (n=29). For all patients (n=50) the 5-year PFS was 80.0% (95% CI 68.7-91.1) and 5-year OS was 84.0% (95% CI 73.8-94.2), as shown in Figures 1 and 2 respectively. 5/10 PFS and 4/9 OS events occurred in patients who had received consolidation IFRT post R-CHOP. Where disease progression occurred 9/10 events occurred within the first-year of follow-up. Conclusion: Our data confirms the efficacy of R-CHOP in the management of PMBL and is a benchmark for future studies in PMBL. This is to our knowledge, the largest reported cohort of R-CHOP treated PMBL patients from a prospective trial. The strength of this analysis lies in the long duration of follow-up, the strict selection of patients according to the WHO 2008 criteria and the inclusion of all patients ≥ 18 years without an upper age limit. In line with previous studies we found that disease progression in PMBL occurs early and late relapses are rare. Over half of the patients in our analysis (58%) received consolidation IFRT following R-CHOP. Response assessment by FDG-PET-CT on completion of R-CHOP was not mandated by the study protocol and whether IFRT could have been avoided for PET negative patients in our cohort is unknown. The currently accruing IELSG 37 prospective trial will help to address this important clinical question in PMBL. Excellent results have recently been reported with the combination of DA-EPOCH-R in PMBL, but the efficacy of such dose-intensified regimens in comparison to R-CHOP needs to be evaluated in prospective randomised studies. Figure 1. Progression Free Survival (n=50) Figure 1. Progression Free Survival (n=50) Figure 2. Overall Survival (n=50) Figure 2. Overall Survival (n=50) Disclosures Cunningham: Amgen: Research Funding; Astra Zeneca: Research Funding; Merck Serono: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Merrimack: Research Funding; Medimmune: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding. Pocock:Janssen: Honoraria.

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.

Introduction of Combined CHOP Plus Rituximab Therapy Dramatically Improved Outcome of Diffuse Large B-Cell Lymphoma in British Columbia

2005 ◽  
Vol 23 (22) ◽  
pp. 5027-5033 ◽  
Author(s):  
Laurie H. Sehn ◽  
Jane Donaldson ◽  
Mukesh Chhanabhai ◽  
Catherine Fitzgerald ◽  
Karamjit Gill ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Ratio ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Survival Risk ◽  
Large B Cell

Purpose For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). Methods We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with “B” symptoms or bulky [> 10 cm] disease) DLBCL. Results A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. Conclusion The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.

scholarly journals Safety and Clinical Activity of Temsirolimus in Combination with Rituximab and DHAP in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma - Report of the Prospective, Multicenter Phase II STORM Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3028-3028
Author(s):  
Mathias Witzens-Harig ◽  
Andreas Viardot ◽  
Ulrich Keller ◽  
Christian Buske ◽  
Anne Crombé ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Free Survival ◽  
Multicenter Phase

Abstract Purpose. To evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL). Methods. This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels of 25, 50, 75 and 100 mg for Temsirolimus were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial. Results. We here report on 46 patients (pts), 15 from part I and 31 from part II. Seven pts were not evaluable for response. Of the evaluable 39 patients, median age was 63 and median number of prior regimen was 1. Temsirolimus dose was 50 mg on day 1 and 8 in 7 pts from the part I of the trial and 25 mg in the remaining 39 pts. The overall response rate was 82% (32/39pts) with 22 partial and 10 complete responses. After a median follow up of 10 months for the total study population, median PFS and OS have not been reached (Figure 1A and 1B). Early safety analysis includes preliminary data of 22 pts. The most frequent non-hematologic side effects were nausea (14 pts, 64%), epistaxis (11 pts, 50%), fatigue (12 pts, 55%), fever (11 pts, 50%) and diarrhea (11 pts, 50%). Frequent grade 3/4 events (n>2) included leukopenia (21 pts, 95%), thrombocytopenia (20 pts, 91%), lymphopenia (11pts, 50%), anemia (8 pts, 36%), neutropenia (10 pts, 45%), renal failure (3 pts, 20%) and infections (7 pts, 32%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). Conclusion. Temsirolimus can be safely added to DHAP and Rituximab with promising activity. Figure 1 Progression free survival Figure 1. Progression free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures Witzens-Harig: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Viardot:Pfizer: Honoraria; Takeda: Other: travel support; Roche: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Spectrum Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees. Buske:Celltrion, Inc.: Consultancy, Honoraria. Meissner:Amgen: Other: Travel Support; Takeda: Other: Travel Support; Teva: Other: Travel Support; Celgene: Other: Travel Support. LaRosee:Pfizer: Honoraria. Marks:Pfizer: Honoraria. Hess:Celgene: Honoraria; Roche, CTI, Pfizer, Celgene: Research Funding; Janssen: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.

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.

scholarly journals Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Electronic Health Record Data ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

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.

Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

Significance of c-myc Rearrangements in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Overall Survival Rates

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.

The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2676-2676
Author(s):  
Jung Yong Hong ◽  
Moon Ki Choi ◽  
Young Saing Kim ◽  
Chi Hoon Maeng ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Clinical Impact ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. Disclosures: No relevant conflicts of interest to declare.

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