Utility of post-therapy surveillance scans in DLBCL.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8504-8504 ◽  
Author(s):  
Carrie A. Thompson ◽  
Matthew J. Maurer ◽  
Herve Ghesquieres ◽  
William R Macon ◽  
Thomas Matthew Habermann ◽  
...  
Keyword(s):  
Medical Records ◽  
Clinical Manifestations ◽  
B Cell Lymphoma ◽  
Post Treatment ◽  
Physical Exam ◽  
Aggressive Lymphoma ◽  
Low Grade ◽  
University Of Iowa ◽  
Post Therapy

8504 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. The optimal follow-up strategy for patients (pts) in remission is not clear. The goal of this study is to determine the utility of surveillance scans in a large, prospective, multi-institutional cohort of DLBCL pts. Methods: Patients were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death with events verified by medical records. Patients eligible for this study had biopsy proven DLBCL and were treated with anthracycline based immunochemotherapy (IC). Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse and relationship to planned follow-up visits and surveillance scans. Results: 644 pts with DLBCL treated with IC were enrolled in MER from 2002-2009. Median age was 63 years (range 18-92), 54% were men, and median f/u was 59 months (range 8-116). 537 pts entered post-treatment observation; 109 (20%) of the 537 pts relapsed and 41 died from other causes. 42% of relapses were in the first 12 months following diagnosis, 27% between 12-24 months, and 31% >24 months. In the 109 who relapsed, 62% of pts (62/100, 9 unknown) presented to their physician earlier than a planned follow-up visit due to symptoms. At the time of relapse, 68% were symptomatic, 42% of pts had abnormal physical exam, and 55% had elevated LDH; 87% of pts had ≥1 of these features. Of the 38 pts with relapse detected at a planned visit, 26 had clinical features of relapse and 12 pts had relapse detected solely by planned surveillance scan; 4 pts had relapse of low-grade or other subtype and 8 had DLBCL relapse (4 of whom had equivocal/positive PET at the end of IC). Thus, surveillance scanning detected DLBCL relapse prior to clinical manifestations in only 8/537 pts (1.5%) observed post DLBCL therapy. Conclusions: The vast majority of DLBCL relapses occur outside of planned follow-up visits and are accompanied by symptoms, physical exam, or laboratory abnormalities. Routine surveillance scans post-therapy add little to detection of DLBCL relapse.

scholarly journals Utility of Routine Post-Therapy Surveillance Imaging in Diffuse Large B-Cell Lymphoma

2014 ◽  
Vol 32 (31) ◽  
pp. 3506-3512 ◽  
Author(s):  
Carrie A. Thompson ◽  
Herve Ghesquieres ◽  
Matthew J. Maurer ◽  
James R. Cerhan ◽  
Pierre Biron ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Clinical Manifestations ◽  
B Cell Lymphoma ◽  
The United States ◽  
Large B Cell Lymphoma ◽  
Surveillance Imaging ◽  
Post Therapy ◽  
Large B Cell

Purpose We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our results in an independent cohort of patients from France. Methods Patients with newly diagnosed DLBCL and treated with anthracycline-based immunochemotherapy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence and the Léon Bérard Cancer Center, Lyon, France. In those with relapse, details at relapse and outcomes were abstracted from records. Results 680 individuals with DLBCL were identified from the MER, 552 (81%) of whom achieved remission after induction. 112 of the 552 patients (20%) suffered a relapse. The majority (64%) of relapses were identified before a scheduled follow-up visit. Surveillance imaging detected DLBCL relapse before clinical manifestations in nine out of 552 patients (1.6%) observed after therapy. In the Lyon cohort, imaging identified asymptomatic DLBCL relapse in four out of 222 patients (1.8%). There was no difference in survival after DLBCL relapse in patients detected at scheduled follow-up versus before scheduled follow-up in both the MER (P = .56) and Lyon cohorts (P = .25). Conclusion The majority of DLBCL relapses are detected outside of planned follow-up, with no difference in outcome in patients with DLBCL detected at a scheduled visit compared with patients with relapse detected outside of planned follow-up. These data do not support the use of routine surveillance imaging for follow-up of DLBCL.

Low-Grade Mucosa-Associated Lymphoid Tissue Lymphoma Involving the Kidney: Report of 3 Cases and Review of the Literature

2006 ◽  
Vol 130 (1) ◽  
pp. 86-89 ◽  
Author(s):  
Libo Qiu ◽  
Pamela D. Unger ◽  
Robert W. Dillon ◽  
James A. Strauchen
Keyword(s):  
Lymphoid Tissue ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Low Grade ◽  
The Third ◽  
First Case ◽  
Abundant Cytoplasm ◽  
History Of

Abstract Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue involving the kidney is rare. We report a series of 3 cases. The first case occurred in an 83-year-old woman who presented with back pain. The second case was a 53-year-old man with a history of sarcoidosis who was found, in the course of evaluation of sarcoidosis, to have a right renal mass. The third case occurred in a 72-year-old man who had a history of periorbital mucosa–associated lymphoid tissue lymphoma and had been treated with surgery and radiation 1 year prior to this presentation. Histologically, all 3 patients showed infiltrate of uniform small-to-medium–sized lymphocytes with irregular nuclear contours and abundant cytoplasm resembling centrocytes or monocytoid lymphoid cells. The first patient received chemotherapy without complications. The second patient underwent a partial nephrectomy and was asymptomatic at the subsequent follow-up. The third patient developed a pulmonary embolism following nephrectomy, and further follow-up is not available.

The IPI Predicts Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: A Report of the University of Iowa/Mayo Clinic SPORE

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1279-1279
Author(s):  
Thomas M. Habermann ◽  
B.K. Link ◽  
M.J. Maurer ◽  
J.E. Wooldridge ◽  
S.M. Geyer ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Predictive Ability ◽  
B Cell Lymphoma ◽  
University Of Iowa ◽  
History Of ◽  
Observational Cohort ◽  
Factor Index ◽  
The Difference ◽  
The University

Abstract The International Prognostic Factor Index (IPI) predicts survival in DLBCL in patients treated with chemotherapy. The Revised IPI (R-IPI) has been reported to be a simpler and more accurate predictor of outcome in patients treated with immunochemotherapy (rituximab and anthracycline-based chemotherapy). We evaluated the predictive value of the IPI and the R-IPI in an observational cohort of unselected patients treated with R-CHOP. Consecutive, newly diagnosed patients age 18 years and older with DLBCL were prospectively offered enrollment into our Lymphoma SPORE Registry. Pathology was centrally reviewed, and composite lymphomas and history of concurrent or prior cancers were excluded. All patients were actively followed for progression free progression (PFS) and overall survival (OS). Here we report on patients enrolled from 9/2002 – 6/2006. 229 patients with a median age of 62 years (range 20–93) were evaluated. 56% were >60 years of age, 16% had a performance score ≥2, 54% had an elevated LDH, 19% had >1 extranodal site, and 51% were stage III/IV. During follow-up, there were 63 progressions (28%) and 45 deaths (20%), and the median follow-up time for living patients was 34 months (range 6–61 months). As shown in the table and figure, the IPI and R-IPI were predictive for both PFS and OS (all p<0.001). The predictive ability of the IPI as measured by 3-year concordance index was stronger for the IPI (0.71) compared to the R-IPI (0.67) and the bootstrap 95% confidence interval for the difference (0.01, 0.08) indicates that this difference was statistically significant. While all factors in the IPI were statistically significant (p<0.05) predictors of OS individually, when included in a multivariate model, an elevated LDH (HR=1.5; p = 0.32) and >1 extranodal sites (HR=1.0; p = 0.96) were no longer significant; similar results were obtained for PFS. The IPI remains a strong predictor of PFS and OS in the immunochemotherapy era. Figure Figure Group % Pats 3 Y PFS HR 95% CI 3 Y OS HR 95% CI Standard IPI Low (0,1) 41% 87% 1.0 ref 93% 1.0 ref Low-Int (2) 22% 62% 3.1 (1.4, 6.8) 74% 4.2 (1.6, 11.1) High-Int (3) 21% 60% 3.1 (1.4, 6.8) 77% 3.4 (1.2, 9.7) High (4,5) 15% 39% 7.2 (3.4, 15.2) 47% 10.2 (4.0, 26.5) R-IPI Very good (0) 11% 96% 1.0 ref 100% 1.0 ref Good (1,2) 53% 74% 6.2 (0.8, 46.0) 84% - - Poor (3–5) 36% 52% 13.5 (1.8, 98.9) 65% - -

Rates and Outcomes of Follicular Lymphoma Transformation in the Rituximab Era: A Report From the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1546-1546
Author(s):  
Brian K Link ◽  
Matthew J Maurer ◽  
Grzegorz S. Nowakowski ◽  
Stephen M Ansell ◽  
William R Macon ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Mayo Clinic ◽  
Cell Lymphoma ◽  
Management Strategies ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
University Of Iowa ◽  
The University

Abstract Abstract 1546 Background: Follicular lymphoma (FL) is an incurable disease with an undefined optimal management strategy. Global priorities in goals of care are avoidance of death and transformation to aggressive subtypes. Retrospective series, – most including patients diagnosed before ubiquitous rituximab use, - describe diverse rates of transformation with a common consensus of 3% per year, and with a median survival post transformation of less than 2 years. This study sought to characterize transformation events in a prospective observational series begun after diffusion of early rituximab use in FL. Methods: Newly diagnosed FL patients were prospectively enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) from 2002–2009. Clinical data were abstracted from medical records using a standard protocol. Patients were actively followed for retreatment, transformation, and death. Inclusion criteria for this analysis were initial diagnosis of grade I-IIIa FL. Exclusion criteria for this cohort include composite diffuse large B-cell lymphoma (DLBCL), FL grade IIIb, or evidence of clinical or pathological transformation at the time of FL diagnosis. Transformation was defined as refractory/recurrent disease with either a) biopsy confirmed subtype of FLIIIb, DLBCL or higher grade B-cell lymphoma; or b) clinical indication of transformation (sudden rise in LDH, rapid discordant localized nodal growth, new involvement of unusual extranodal sites, new B symptoms or hypercalcemia). Risk of transformation was analyzed via time to transformation using a death as a competing risk. Time to transformation was defined as the date of initial FL diagnosis to date of transformation. Overall survival was defined as the date of initial diagnosis to date of death or last known follow-up for patients still alive. Results: There were 631 newly diagnosed grade I-IIIa FL patients with a median age at enrollment of 60 years (range 23–93). 54% were male. The most common types of initial therapy were observation (33%), rituximab (R) monotherapy (12%), alkylator based chemotherapy +/− R (22%), and anthracycline based chemotherapy +/− R (20%). At a median follow-up of 60 months (range 11–110), 79 patients had died, 311 patients had an event (death, progression, or retreatment), and 60 patients (9.5%) had transformed. Transformation was biopsy proven in 48 of the 60 patients (80%). The overall transformation rate at 5 years (TX5) was 10.7% (95% CI: 8.3%–13.8%) (Figure 1). Time to transformation was associated with a FLIPI score of 3–5 (HR=2.37, 95% CI 1.28–4.39, p=0.006), but was not significantly associated with other standard clinical characteristics. Risk of transformation was different in the common initial treatment groups with the highest rate in patients who were initially observed (TX5=14.4%) and lowest rate in patients who initially received R monotherapy (TX5=3.2%)(p=0.058). Outcome after transformation was inferior to MER subjects with de-novo diagnosed DLBCL (p<0.0001). The median overall survival from date of transformation was 44 months (95% CI: 22-NA). Survival after transformation was superior in patients who transformed greater than 18 months after FL diagnosis compared to patients who transformed earlier (5 yr OS =70% vs 20%) (p=7 ×10−5), and for those initially observed (median unreached) versus those patients who were initially treated with alkylator or anthracycline based chemotherapy (median survival of 11 months)( p=0.016). Conclusions: Follicular transformation rates in this modern large prospective observational study are similar to risk of death without transformation and slightly lower at 5 years than most previous reports. Post-transformation prognosis is substantially better than described in older series. These observed differences may be a function of the prospective nature of the study design, modern management strategies, or patient selection factors. Initial management strategies may influence the risk of transformation. Marked survival differences following early vs. late transformation suggest that these may be different biologic events. Disclosures: Link: Genentech: Consultancy, Research Funding; Celgene: Consultancy; Millenium: Consultancy. Johnston:Novartis: Consultancy.

Non-Follicular Low Grade B-Cell Lymphomas: Patterns of Presentation and Management with Comparative Prognostic Utility of IPI and FLIPI

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1563-1563
Author(s):  
Laura S. Jacobus ◽  
Julianne Lunde ◽  
Matthew J Maurer ◽  
Ahmet Dogan ◽  
Sergei I Syrbu ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
University Of Iowa ◽  
Prognostic Utility ◽  
The University

Abstract Abstract 1563 Intro: Optimal treatment for non-follicular low grade B-cell lymphoma (NFLGL) is not well defined. Clinical trial design for these subtypes would be enhanced by further understanding of early presentation and management. A large prospective observational study was used to identify presenting clinical features, describe patterns of care and compare the prognostic utility of International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI). Methods: The University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) is a prospective, longitudinal observational study designed to collect information on patterns of care and outcomes for patients with newly diagnosed lymphoma. Patients seen at the Mayo Clinic, Rochester MN and the University of Iowa within 9 months of their initial diagnosis of lymphoma are offered enrollment. Baseline patient reported data, clinical data and initial management are collected using a standard protocol and a central pathology review is performed. After enrollment, patients are actively followed for events (disease progression, retreatment, and death) and disease related comorbidities. This analysis includes 198 patients diagnosed with extranodal marginal zone (EMZL), 22 with nodal marginal zone (NMZL), 47 with splenic marginal zone (SMZL), 48 with lymphoplasmacytic lymphoma (LPL), as well as 67 patients with unclassifiable low-grade B-cell lymphoma (B-NOS). Results: 382 newly diagnosed NFLGBL patients were enrolled in the MER from 2002–2009. The median age at enrollment was 63 years (range 22–95). 52% were male. The most common types of initial therapy after diagnosis were observation (41 %), alkylator- based chemotherapy +/− rituximab (R) (17%), radiation therapy alone (15%) and R monotherapy (13%). At median follow-up of 60 months (range 1–121), 51 patients were deceased and 155 had an event. The clinical characteristics that comprise the IPI and FLIPI were similar across the subtypes. Approximately half of the cases presented at low risk (55% IPI; 48% FLIPI). A majority had a normal LDH (81%), limited nodal involvement (91% had ≤ 4 groups), normal hemoglobin (71% ≥12 g/dL), good performance status (95% 0–1), and advanced stage (57% stages III-IV). There were notable differences among the NFLGBL subtypes. Patients with SMZL and LPL presented with high risk FLIPI of 3–5 (49% and 46% respectively) and high to high-intermediate IPI of 3–5 (21% and 13%). Abnormal LDH and anemia (< 12 g/dL) were more frequent in patients with SMZL (40%; 56%) and LPL (25%; 62%). EMZL presented with lower stages (70% stage I-II) and NMZL presented with increased nodal involvement (38% >4 sites). SMZL had the highest rates of surgical resection (21%) and EMZL was more frequently treated with radiation therapy (25%). LPL (30%) and NMZL (32%) more commonly received alkylator based chemotherapy +/− R. While both IPI and FLIPI differentiated outcome in these patients, FLIPI had higher c-statistics than IPI for both EFS (0.583 vs 0.568) and OS (0.685 vs 0.661), respectively. Conclusions: This large prospective collection of data on NFLGBL patients presenting to academic medical centers provides a modern picture of presentation and management patterns useful to investigators designing clinical trials. FLIPI may have more prognostic utility than IPI in this group of patients. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding.

Intensified Rituximab Induction Followed By Rituximab Maintenance For Low Grade B Cell Lymphoma: A Multicenter, Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1797-1797
Author(s):  
Kyouhei Yamada ◽  
Morio Sawamura ◽  
Takeshi Shimomura ◽  
Makoto Takeuchi ◽  
Shuichi Hanada ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Rituximab Maintenance ◽  
Multicenter Phase

Abstract Introduction Rituximab has markedly improved the clinical outcomes of mature B cell lymphoma, and rituximab maintenance therapy has been shown to be beneficial, especially in low grade B cell lymphoma (LGBCL). Several studies evaluated intensified rituximab administration combined with chemotherapy. But so far, there has not been any trial of rituximab mono-therapy with intensive rituximab induction followed by maintenance. A multicenter, phase II trial was conducted to evaluate the efficacy and safety of rituximab as induction, weekly 8 doses, and maintenance therapy for 2 years for LGBCL. Patients and Methods Patients with measurable LGBCL according to the World Health Organization (WHO) classification (2001) without prior rituximab treatment and staged as II, II, or IV by Ann-Arbor, were eligible. Patients received rituximab (375 mg/m2) weekly for 8 weeks as induction therapy, and then patients who did not have progressive disease at the end of induction received maintenance therapy with 4 weeks of rituximab at six-month intervals (up to 2 years or disease progression). Duration of treatment was 2.5 years in total. The primary endpoint was the best overall response rate (ORR). The secondary endpoints were complete response rate (CRR), 3-year progression free survival (PFS), 3-year overall survival (OS), and safety. Survivals were assessed using the Kaplan-Meier method. Results Forty-one patients with a median age of 64 years (41 to 79) were enrolled at 12 institutes belonging to the Clinical Hematology Group of National Hospital Organization (CHG-NHO) of Japan from December 2005 to May 2009. The majority of disease histology was follicular lymphoma in 33 patients. Of 41 patients, 15 were diagnosed as high tumor burden based on GELF criteria, and FLIP risk grouping classified all into 12 low risk, 21 intermediate risk, and 12 high risk cases. Four relapsed cases were included, and they have all received prior systemic chemotherapy without rituximab. Of the 41 patients, 31 (75.6%) completed the planned 2.5 years therapy. The best ORR was 75.6% (31/41, 90% CI: 62.2-86.1%), with 63.4% CR. Three-year PFS at a median follow-up time of 43.0 months (5.3-72) was 79.7% (90% CI, 66.6-88.1%). Three-year OS at a median follow-up time of 49.4 months (5.3-72) was 97.4% (90% CI, 87.1-99.5%). Grade 3 toxicities were neutropenia in 2.5% (1/41), elevated ALT in 2.5% (1/41), and infection in 2.5% (1/41). There was no grade 4 toxicity. Conclusions Intensified rituximab induction and maintenance therapy was demonstrated to have high activity, with durable PFS and minimum toxicity in LGBCL patients. Although a further large-scale trial is needed, intensified rituximab induction followed by rituximab maintenance could be a good treatment in rituximab naïve LGBCL. Disclosures: No relevant conflicts of interest to declare.

Interim Positron Emission Tomography-Computed Tomography (PET-CT) Is Predictive of Post-Therapy Outcome in High Grade Transformation of Low Grade Lymphoproliferative Disorders

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5038-5038
Author(s):  
Louise Imlay-Gillespie ◽  
David Simon Kliman ◽  
Kelly Wong ◽  
Christopher Arthur ◽  
Luke Coyle ◽  
...  
Keyword(s):  
Research Funding ◽  
Metabolic Response ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Interim Pet ◽  
Pet Ct ◽  
High Grade Transformation ◽  
Post Therapy ◽  
Initial Staging

Abstract Background PET-CT has become an essential tool in the management of Lymphoma. PET-CT is utilized in both the initial staging of lymphoma as well as assessing treatment-response. High grade transformation of a low grade lymphoproliferative disorder (LPD) is associated with a poor prognosis. Patients (pts) are usually treated with standard of care for Diffuse Large B-Cell Lymphoma (DLBCL) with R-CHOP but generally have poorer outcomes and can experience relapse of either low or high grade disease. To our knowledge, PET-CT has not been evaluated as a prognostic tool for the subgroup of transformed DLBCL. Methods A retrospective audit was performed of patients treated at Royal North Shore Hospital in Sydney, Australia between 2003-2012. Pts were included if they were treated with Rituximab for DLBCL during the study period and if this occurred on a background of low-grade LPD. Clinical data including LPD type, initial staging, treatment and outcomes were also collected. Treatments were stratified into standard R-CHOP-like versus more intensive regimens including Hyper-CVAD and dose-adjusted R-EPOCH. PET-CT reports were reviewed at staging, interim and post-therapy time points and outcomes stratified to complete metabolic response (CR), partial metabolic response (PR) and progressive disease (PD),based on the nuclear medicine physician's report. Results 64 pts were identified in the study period with median follow up 4.4 yrs (range, 50d-11yrs)Male:female ratio was 1:1. Median age was 65 yrs (range 30-89). LPD diagnosis included Follicular Lymphoma (FL) (75%), Chronic Lymphocytic Leukemia (CLL) (6%) and others (19%) that included Mucosa Associated Lymphoid Tissue and Marginal Zone Lymphomas. 39 pts (61%) had PET-CT reports available for review. 45 pts (70%) were treated with R-CHOP with the remainder having more intensive regimes. 26% of pts received consolidation radiotherapy. 13 pts (20%) underwent autologous and 6 (9%) proceeded to an had an allogeneic transplant. 3 yr OS and EFS was 89% and 73% respectively. Univariate analysis demonstrated both interim and post therapy PET-CT to be significant for both OS and EFS (p<0.01) with three groups identified; CR, PR and PD with 3 year OS for negative interim PET of 100%, 91% and 0% accordingly. CR on end of therapy CT was associated with improved OS (p<0.05) but not interim CT (p=0.967). On multivariate analysis interim PET-CT was the strongest independent predictor for EFS but not OS (p < 0.05). Discussion PET-CT is an invaluable tool in the management of LPD. This retrospective review demonstrates the utility of interim PET-CT in the prognostication of pts with transformed LPD. Larger prospective studies should be considered using PET-CT to more accurately stratify treatment for pts with transformed LPD. Figure 1. Figure 1. Disclosures Imlay-Gillespie: Novartis: Honoraria. Arthur:Amgen: Honoraria; Amgen: Honoraria; BMS: Honoraria. Mackinlay:Sanofi Aventis: Research Funding; Roche: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Molecular Characterization of Diffuse Large B-Cell Lymphoma Associated to Hepatitis C Virus Infection

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2402-2402
Author(s):  
Roberta Sciarra ◽  
Caterina Cristinelli ◽  
Michele Merli ◽  
Marco Lucioni ◽  
Silvia Zibellini ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Immune Regulation ◽  
Research Funding ◽  
Notch Pathway ◽  
B Cell Lymphoma ◽  
Fish Analysis ◽  
Low Grade ◽  
Advisory Committees

Abstract BACKGROUND. HCV-positive DLBCL has distinct clinical and pathologic characteristics compared to its negative counterpart: patients (pts) are usually older with more frequent splenic and extranodal involvement and elevated LDH. Differently from its clinical hallmarks, the molecular landscape of this pathological entity has been scarcely outlined. METHODS. In this bicentric study, we investigated the clinical and molecular features and outcome of 54 pts with HCV-positive DLBCL. Targeted next generation sequencing (NGS) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue biopsies. A core panel probes covering coding exons from 184 genes frequently mutated in mature B cell neoplasms was designed using IDT tool and libraries were prepared using Illumina DNA-prep-with enrichment. Sequencing was performed on Illumina HiSeq 2500. Cluster analysis was performed using LymphGen tool. We also applied fluorescence in situ hybridization (FISH) for MYC, BCL2 and BCL6. RESULTS. Median age was 71 (33-84; IQR: 61.9-77). Stage was III/IV in 34 pts (63%). Extranodal sites were involved in 21 pts (38%), spleen in 20 pts (37%). LDH was higher than the upper limit in 40 pts (74%). R-IPI was good for 2 pts (4%), intermediate for 24 pts (44%), poor for 28 pts (52%). HPS score was intermediate or high in 33 of 44 assessed pts (75%). A histological low-grade component was identified in 15 pts (27%). Hans algorithm differentiated pts almost equally in GCB (26/50, 52%) and non-GCB (24/50, 48%) subtype. HCV-RNA was detectable in 52 pts (96%) and quantifiable in 43 pts (79%). Of 29 pts assessed, genotype was 1 in 9 (31%), 2 in 16 (55%), 3 in 4 pts (14%). Among 37 pts whose data were available, 11 pts (30%) received direct antiviral agents, 7 pts (19%) received interferon-containing regimen, 19 pts (51%) were not treated for HCV. Twenty-seven pts (50%) received rituximab-enriched protocols, 23 pts (43%) were treated with chemotherapy alone, 1 pt (2%) with surgery alone, 3 pts (5%) were lost to follow up. With a median follow up of 7.7 years (yrs) (IQR: 4.6-10.6), 5-yrs overall survival (OS) (95%CI) was 49.3% (34.1-62.8%) and 5-yrs progression free survival (PFS) (95%CI) was 39.5% (25.5-53.3%). Median OS and PFS were 4.9 and 3.1 yrs, respectively. FISH analysis showed lack of BCL2 (0/19) and MYC translocations (0/15). BCL6 fusions were found in 76% of pts (16/21). NGS showed mutations in 154 of the 184 analyzed genes. The informativity of the panel was 100% with all pts presenting at least one oncogenic variant. Gene mutation frequencies are presented in Fig. 1. The median mutation load (MML) was 13 mutated genes per case (2-32; IQR: 9-16). Most frequently mutated genes were the epigenetic regulators KMT2D, mutated in 23 pts (42.6%), and SETD1B, mutated in 17 pts (31.5%). FAS, PM1 and RERE were mutated in 15 pts each (27.8%). TBL1XR1, BCL11A and SGK1 were mutated in 14 (26%), 13 (24%) and 12 pts (22%), respectively. Considering genes in their specific pathway, 94% of pts harbored mutations in genes involved in epigenetic regulation (MML: 3; range 1-7; IQR: 1.25-4), 90% of pts in apoptosis-related genes (MML: 2; 1-7; IQR: 1-3) and 77% of pts in genes belonging to BCR/NFkB signaling pathway (MML: 2; 1-7; IQR: 1-3). Of note, 56% of pts carried mutations in genes related to immune regulation (MML: 1.7; 1-5; IQR: 1-2) and 25% of pts had mutations within the NOTCH pathway (MML: 1.2; range 1-2). Via the LymphGen 1.0 tool, we classified 26 pts (48%) into 4 genetic clusters: BN2 (11/26, 42%), ST2 (8/26, 31%), MCD (4/26, 15%), EZB (3/26, 12%). Twenty-eight pts (52%) were classified as "others". Among those belonging to BN2 cluster, 7 pts (64%) had a histologically confirmed transformed DLBCL. No significant differences in terms of OS and PFS were identified according to cluster subgroups. CONCLUSIONS. The prevalence of the BN2 cluster and enrichment of mutations of genes involved in NOTCH pathway seem to indicate a preferential marginal-zone origin in HCV-positive DLBCL. In addition, our data confirm the absence of BCL2 translocation in this subset of DLBCL and show a high prevalence of mutated genes within the epigenetic and immune regulation pathways in HCV-positive DLBCL, pointing out their compelling role in the pathogenesis and suggesting potential implications for molecularly targeted therapies. Figure 1 Figure 1. Disclosures Passamonti: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arcaini: Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses.

scholarly journals Spontaneous Remission of Diffuse Large B Cell Lymphoma in the Stomach and the Continuation of Remission for 10 Years

2018 ◽  
Vol 12 (3) ◽  
pp. 699-703 ◽  
Author(s):  
Toshiro Sugiyama ◽  
Kotaro Arita ◽  
Eiji Shinno ◽  
Takahiko Nakajima
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Spontaneous Remission ◽  
Aggressive Lymphoma ◽  
Large B Cell Lymphoma ◽  
First Remission ◽  
Helicobacter Pylori Treatment ◽  
Large B Cell

According to the literature, spontaneous remission of aggressive lymphomas is extremely rare; gastric non-Hodgkin lymphomas, such as mucosa-associated lymphoid tissue lymphomas, often regress due to Helicobacter pylori treatment or no progression, even in a watch-and-wait strategy. Although spontaneous remission of diffuse large B cell lymphomas in the stomach was very rarely reported, the follow-up periods of the cases of spontaneous remission are within 2 years and most cases are likely to relapse after the first remission. Here, we report that a diffuse large B cell lymphoma in the stomach showed spontaneous remission within 2 months after the initial diagnosis and the remission is still continuing for 10 years without any specific treatments against this aggressive lymphoma.

IgM-Secreting Diffuse Large B-Cell Lymphoma (DLBCL) Is a Poor Prognostic Subset within the Non-Germinal-Centre-Type (GC-type): An Italian Multicentre Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-31
Author(s):  
M. Christina Cox ◽  
Luigi Marcheselli ◽  
Gerardo Musuraca ◽  
Maria Cantonetti ◽  
Carlo Visco ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Board Of Directors ◽  
B Cell Lymphoma ◽  
Independent Prognostic Factor ◽  
Biological Study ◽  
Low Grade ◽  
Advisory Committees ◽  
Bulky Disease ◽  
Prognostic Features

BACKGROUND: In 2014 we identified a new subset of DLBCL, defined as "IgM-secreting" (Cox MC & Di Napoli A , PLOS One 2014). This was characterised by poor prognostic features and outcome as well as frequent central nervous (CNS) system localizations. Furthermore, IgM-secretion, was an independent prognostic factor in multivariate analysis. Here we report on the largest series of IgM-secreting-DLBCL, from a multicentre Italian study. METHODS: The observational and biological study was approved by the Ethical Committee of the AUO Sant'Andrea, Italy. Enrolment criteria were: DLBCL with an associated IgM paraprotein diagnosed between 1st January 2010 and 31st December 2018 (IgM-secreting). Data were collected both prospectively and retrospectively from 17 Centres participating in the study. In addition, histopathology samples were centrally revised for immunohistochemistry (IHC) and FISH analyses. The control group (CTRL) consisted in a series of consecutive DLBCL, without an associated IgM-paraprotein (diagnosed between 01/01/2013 and 30/06/2016, enrolled in the Lymphoma Registry of the Lazio region (ReLLi Network). Last follow-up was carried out on 31st December 2019. RESULTS: 569 DLBCL cases were enrolled: 102 (17.9%) were IgM-secreting; 48 (8.4%) had a non-IgM paraprotein (IgA, IgG, or other), and 414 (72.7%) had no associated paraprotein (CTRL). IgM-secreting cases within the consecutive DLBCL patients enrolled in the ReLLi Registry were 41/466 (8.8%, 95CI 6.4-11.7%) while non IgM-paraprotein DLBCL cases were 11/466 (2.4%, 95CI 1.2-4.2%). The median level of IgM paraprotein was 17gr/L (range: &lt;1-84gr/L); 83/102 (81.3%) were IgMk and 23/102 (22.5%) IgML respectively. The IgM-secreting group differed from the CTRL because the following characteristics were significantly more frequent: 1] age&gt;60 (p=.001); 2] advanced stage (p&lt;.001); 3] PS≥2 (p=.001); 4] LDH&gt;UNL (p=.008) ; 5] ≥2 Extra-nodal sites involved (p&lt;.001) ; 6] IPI 3-5 (p&lt;.001); 7] central nervous system (CNS) involvement at diagnosis or relapse (p&lt;.001); 8] lower rate of complete remission(CR) at the end of induction immunochemotherapy (p&lt;.001). Conversely, no differences were observed for: sex, B-symptoms, HCV and HBV status, bulky disease, age≥80 years, and for transformation from low-grade lymphoma. PATHOLOGICAL AND MOLECULAR FEATURES: Paraffin tissue from 74 CTRL and 69 IgM-secreting was suitable for immunohistochemistry (IHC). The non-GCB subtype, based on Hans algorithm, was prevalent in the IgM-secreting (p=.005). No difference in BCL2 expression alone or in MYC and BCL2 double expression was observed within groups. In 48/63(76%; 95CI: 64-86%) IgM-secreting cases, both the IgM heavy and the corresponding kappa or lambda light chain protein expression were detected in the cytoplasm of the neoplastic clone. FISH analyses for MYC, BCL2 and BCL6 genes rearrangements performed in 25 IgM-secreting cases with either expression of MYC protein or a GC-phenotype showed no evidence of double or triple hits (DH/TH). TREATMENT: in the IgM-secreting group more patients were treated with RCOMP and with less intensive approach than the CTRL (p&lt;.001). SURVIVAL: The median follow-up time was 46 months (95CI= 44-49; range 18-101) with 130 events and an incidence rate x100 person/year of 7.22 (95%CI 6.08-8.58) and a 5-yr OS of 76% (95CI 72-79%). The 5-PFS was 61% (95CI 57-65%). In univariable analysis age&gt;60, B-symptoms, bulky disease, IPI &gt;low risk and IgM-secreting IgM showed a worse survival (all with p&lt;0.001). Also, the IgM-secreting group, showed a worse survival compared to the DLBCL with an associated IgG/IgA paraprotein (p&lt;0.001). Adjusting in multiple Cox regression, IgM-secreting with IPI, gender, bulky and B-symptoms, maintain a higher risk of death either in the all cohort (HR 1.93, 95CI 1.34-2.78, p&lt;0.001) or in patients with age&lt;80 (HR 1.71, 95CI 1.16-2.54, p=0.007). Noteworthy, a survival sub-analysis showed that the 12/69 (17.4%) IgM-secreting with a GC-type had a better OS (9=0.008) and PFS (p=0.002) compared to the 57/69 (82.6%) IgM-secreting with a non-GC-type. CONCLUSION: Our data confirm that IgM-secreting DLBCL: 1) represents a sizable proportion of non-DH DLBCL; 2) have poor prognostic features and 3) have mostly a non-GC phenotype. Furthermore, IgM secretion appears to be an independent prognostic factor for both PFS and OS. Studies to define the biological features of this new subset are ongoing. Disclosures Cantonetti: Mundipharma: Consultancy; Takeda: Consultancy; Vifor: Consultancy; Roche: Consultancy. Re:BerGenBio ASA: Research Funding. Abruzzese:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.

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