scholarly journals The Effect of Therapy on High Grade B Cell Lymphoma, Not Otherwise Specified and Outcomes in Comparison with Double Hit Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4224-4224 ◽  
Author(s):  
Jonathan Rush ◽  
Alison R. Sehgal ◽  
Christine G. Roth ◽  
Michael Boyiadzis
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Standard Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
University Of Pittsburgh ◽  
Double Hit Lymphoma ◽  
Double Hit ◽  
The University

Abstract Background: High grade B cell lymphoma (HGBL) is a heterogeneous entity with morphologic and genetic features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BL). Many patients with HGBL also have concurrent MYC, BCL2 and/or BCL6 rearrangements documented by FISH, the so-called double-hit lymphoma (DHL), which has now been defined as a separate entity in the updated WHO classification in 2016 as HGBL with rearrangements of MYC and BCL2 and/or BCL6. Other HGBL without MYC and BCL2 or BCL6 have been termed HGBL, NOS. HGBL, NOS and DHL are considered clinically aggressive. The best therapeutic approach for HGBL, NOS is unclear, and outcomes of patients with DHL in comparison to HGBL, NOS are not well established. Objective: The aim of this study was to evaluate and describe the outcomes and practice patterns for patients with HGBL, NOS. Additionally, we compared the survival of patients with HGBL, NOS to those with DHL. Materials and Methods: This retrospective cohort study was conducted at the University of Pittsburgh Medical Center. All patients identified as HGBL by pathology review at the University of Pittsburgh Hematopathology Department from 2010-2014 were included. Outcomes between standard therapy with R-CHOP and high intensity therapies with either R-EPOCH or R-HyperCVAD were compared for those patients with HGBL. Survival curves were generated with the Kaplan-Meier method, and overall survival was compared using the log-rank test. Cox-regression analysis was used to adjust for covariates. Results: 50 patients with newly diagnosed HGBL without a double-hit genotype were identified. Of these patients, 38 received R-CHOP (63%), R-EPOCH (21%) or R-HyperCVAD (16%). Baseline characteristics between treatment groups (Table 1) revealed an older age (p=0.033) and more frequent germinal center genotype (p=0.023) in those treated with R-CHOP. Median follow-up for this group was 18 months. There was no difference in the overall survival (OS) between R-CHOP and higher intensity regimens (p=0.540) (Figure 1). Median survival was not reached in either group. 2-year survival was 76%. Only a high-risk IPI score retained prognostic significance with OS in multivariate analysis (p=0.022). This compares favorable to 13 cases of DHL treated with R-CHOP, R-EPOCH, or R-HyperCVAD during a similar time period for whom the median overall survival was 8.9 months (p=0.016) Conclusion: Both standard therapy with R-CHOP and higher intensity therapies appear to be effective in the treatment of HGBL without double-hit genotype. IPI score remains prognostically significant. Outcomes in patients with HGBL, NOS appear favorable in comparison with patients with DHL. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Challenges and Opportunities for High-grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangement (Double-hit Lymphoma)

2019 ◽  
Vol 42 (3) ◽  
pp. 304-316 ◽  
Author(s):  
Dongfeng Zeng ◽  
Aakash Desai ◽  
Fangfang Yan ◽  
Tiejun Gong ◽  
Haige Ye ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Double Hit Lymphoma ◽  
Challenges And Opportunities ◽  
Double Hit

scholarly journals High-grade B-cell Lymphoma with MYC and BCL2 Rearrangement Arising from Follicular Lymphoma: Presentation as a Large Peripancreatic Mass

Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 157
Author(s):  
Anna Shestakova ◽  
Sherif Rezk ◽  
Dara Ghasemizadeh ◽  
Ali Nael ◽  
Xiaohui Zhao
Keyword(s):  
Lymph Node ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
Inguinal Lymph Node ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Double Hit Lymphoma ◽  
Double Hit

Follicular lymphoma, the second most common non-Hodgkin lymphoma (NHL), primarily affects adults and shows an indolent clinical course. Rare cases of follicular lymphoma transform to a high-grade B-cell lymphoma with MYC and BCL2 rearrangements or “double-hit lymphoma”. Transformation to a “double-hit lymphoma” portends a worse prognosis and requires aggressive treatment. We report a comprehensive clinical, pathologic and radiographic review of a patient with previously undiagnosed low-grade follicular lymphoma that transformed into a “double-hit lymphoma”. The patient presented with a large heterogeneous mass 16 x 19 cm involving pancreatic head and neck and a mildly enlarged inguinal lymph node. Positron emission tomography (PET) study demonstrated Fluorodeoxyglucose (18F) (FDG)-avid peripancreatic mass. Tissue biopsy demonstrated a high-grade B-cell lymphoma with rearrangements t(14;18) and MYC, leading to the diagnosis of high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Excisional biopsy of an inguinal lymph node demonstrated low-grade follicular lymphoma. Clonality studies demonstrated the same immunoglobulin clone V7-4 in inguinal lymph node and peripancreatic mass. Therefore, diagnosis of a high-grade B-cell lymphoma with MYC and BCL2 rearrangements that transformed from a low-grade follicular lymphoma was rendered. It is ultimately important to establish a tissue-based diagnosis at the different sites that are involved with lymphoma. Patient proceeded with the aggressive treatment with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) treatment.

scholarly journals How I treat double-hit lymphoma

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

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

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.

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

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

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

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.

“Double-Hit” Cytogenetic Status Is Not Predicted By Baseline Clinicopathologic Characteristics and Is Highly Associated With Overall Survival In B Cell Lymphoma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4338-4338
Author(s):  
Daniel J. Landsburg ◽  
Sunita Dwivedy Nasta ◽  
Jakub Svoboda ◽  
Jennifer JD Morrissette ◽  
Stephen J. Schuster
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Gene Rearrangement ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Rearrangements ◽  
Myc Gene ◽  
Double Hit ◽  
The Impact

Abstract Background “Double-Hit” (DH) lymphomas are most commonly defined as B cell lymphomas demonstrating a MYC gene rearrangement and additional rearrangement(s) involving BCL2 and/or BCL6. DH lymphomas respond poorly to standard immunochemotherapy regimens, often prompting the use of more intensive treatments. DH gene rearrangements can be identified through metaphase cytogenetic testing or more sensitive fluorescence in situ hybridization (FISH) on diagnostic tissue specimens, although these studies are not routinely performed. Here, we analyze a cohort of B cell lymphoma patients to determine whether DH status can be predicted by clinicopathologic features as well as the impact of DH status on survival. Methods Fifty-three patients diagnosed with B cell lymphoma treated at the University of Pennsylvania from 2006-2013 who underwent diagnostic FISH for MYC gene rearrangements using probes to detect either an 8q24 split or t(8;14) were included in this analysis. FISH was performed at request of the interpreting pathologist or treating clinician. Patients with classic Burkitt lymphoma were excluded. Cases of DH lymphoma (DH+) were defined as demonstrating at least one of either 8q24 split, t(8;14), t(2;8) or t(8;22) as well as a BCL2, BCL6 and/or BCL1 rearrangement. Therapy was given at the discretion of the treating clinician. Response was defined using the Revised Response Criteria for Malignant Lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-86.). Results DH+ was detected in 17 patients (32%) and a sole MYC gene rearrangement was detected in an additional 9 patients (17%). MYC gene rearrangements were detected by metaphase cytogenetics in 4 (15%) and by FISH in 22 (85%) of these patients. No factor, including age, LDH, stage, International Prognostic Index (IPI) or histology was predictive of DH status (Table I). DH+ patients were treated with R-hyperCVAD (41%), R-CHOP (41%) and other regimens (18%). Complete response was less frequent in DH+ compared to non-DH patients (41% vs. 81%, p=0.002). With a median follow-up of 10.4 months (range 1.2-72.4), the median overall survival was significantly shorter for DH+ compared to non-DH patients (8.2 vs. 56.8 months, p<0.001). Median overall survival was not significantly different for non-DH patients with and without a sole MYC gene rearrangement (50.8 months vs. not yet reached, p=0.33). Univariate Cox regression analysis showed that the presence of a MYC gene rearrangement (MYC+) and DH+ had statistically significant associations with overall survival; however, only DH+ retained statistical significance on multivariate analysis (Table II). Conclusions DH status cannot be inferred by baseline disease- or patient-related characteristics and is most predictive of overall survival in this cohort of B cell lymphoma patients. These findings support the practice of routine FISH for DH gene rearrangements in order to better identify DH+ patients who may benefit from risk-adapted and/or targeted therapies. We plan to validate our findings in a larger unselected cohort of diffuse large B cell lymphoma patients. Disclosures: No relevant conflicts of interest to declare.

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