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https://www.readbyqxmd.com/read/28196522/xpo1-in-b-cell-hematological-malignancies-from-recurrent-somatic-mutations-to-targeted-therapy
#1
REVIEW
Vincent Camus, Hadjer Miloudi, Antoine Taly, Brigitte Sola, Fabrice Jardin
Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies...
February 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28194060/retrospective-study-of-pegaspargase-gemicitabine-oxaliplatin-and-dexamethasone-peg-gemod-as-a-first-line-therapy-for-advanced-stage-extranodal-nk-t-cell-lymphoma
#2
Yi-Yun Yao, Yong Tang, Yan Zhuang, Li-Fang Zou, Hong-Ju Dou, Lei Wang, Qi Zhu
This study was conducted to retrospectively investigate the efficacy and safety of pegaspargase, gemicitabine, oxaliplatin and dexamethasone (Peg-GemOD) combination chemotherapy as a first-line therapy for advanced-stage extranodal NK/T cell lymphoma (ENKTL). Eighteen patients with newly diagnosed stage III/IV ENKTL were subjected to 3-6 cycles of Peg-GemOD chemotherapy. After 3 cycles of therapy, the overall response rate was 67 % (12/18) with a complete response rate of 28 % (5/18) and a partial response rate of 39 % (7/18)...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28188172/t-cell-repertoires-in-refractory-coeliac-disease
#3
Julia Ritter, Karin Zimmermann, Korinna Jöhrens, Stefanie Mende, Anke Seegebarth, Britta Siegmund, Steffen Hennig, Kremena Todorova, Andreas Rosenwald, Severin Daum, Michael Hummel, Michael Schumann
OBJECTIVE: Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis...
February 10, 2017: Gut
https://www.readbyqxmd.com/read/28096087/diffuse-large-b-cell-lymphoma-genotyping-on-the-liquid-biopsy
#4
Davide Rossi, Fary Diop, Elisa Spaccarotella, Sara Monti, Manuela Zanni, Silvia Rasi, Clara Deambrogi, Valeria Spina, Alessio Bruscaggin, Chiara Favini, Roberto Serra, Antonio Ramponi, Renzo Boldorini, Robin Foa', Gianluca Gaidano
Accessible and real-time genotyping for diagnostic, prognostic or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. Here we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pre-treatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with a >90% sensitivity and a ~100% specificity...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/27943278/frequency-and-clinical-correlates-of-elevated-plasma-epstein-barr-virus-dna-at-diagnosis-in-peripheral-t-cell-lymphomas-ptcl
#5
Bradley M Haverkos, Ying Huang, Alejandro Gru, Preeti Pancholi, Aharon G Freud, Anjali Mishra, Amy S Ruppert, Robert A Baiocchi, Pierluigi Porcu
Epstein Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact, and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients...
December 10, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#6
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27917702/effectiveness-of-pegaspargase-gemcitabine-and-oxaliplatin-p-gemox-chemotherapy-combined-with-radiotherapy-in-newly-diagnosed-stage-ie-to-iie-nasal-type-extranodal-natural-killer-t-cell-lymphoma
#7
Wen Wei, Ping Wu, Li Li, Zhi-Hui Zhang
PURPOSE: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct subtype of non-Hodgkin lymphoma. ENKTL is sensitive to radiotherapy, but the prognosis is poorer than those of other types of early stage lymphoma. To date, optimal treatment strategies for patients with early stage ENKTL have not been fully defined. METHODS: We retrospectively investigated the efficacy and safety of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) combined with different dose radiotherapy (RT) in the treatment of 35 newly diagnosed, stage IE to IIE ENKTL patients at our institution from October 2011 to September 2015...
December 5, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27831904/distinct-biological-subtypes-and-patterns-of-genome-evolution-in-lymphoma-revealed-by-circulating-tumor-dna
#8
Florian Scherer, David M Kurtz, Aaron M Newman, Henning Stehr, Alexander F M Craig, Mohammad Shahrokh Esfahani, Alexander F Lovejoy, Jacob J Chabon, Daniel M Klass, Chih Long Liu, Li Zhou, Cynthia Glover, Brendan C Visser, George A Poultsides, Ranjana H Advani, Lauren S Maeda, Neel K Gupta, Ronald Levy, Robert S Ohgami, Christian A Kunder, Maximilian Diehn, Ash A Alizadeh
Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects...
November 9, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27784363/-quantitation-of-circulating-cell-free-dna-in-patients-with-lymphoma-and-its-clinical-significance
#9
Yuan-Yuan Chen, Su-Qing Guo, Ying-Hua Li, Dong-Mei Wang, Xiao Liu, Yong-Xiao Zhang, Shu-Ye Wang
OBJECTIVE: To evaluate the value of circulating cell-free DNA (CFDNA) quantification for screening lymphoma, to analyse the relationship of circulating CFDNA with curative effect under standard therapeutic schedule, and to determine whether circulating CFDNA could be applied to monitor and prognosticate lymphoma. METHODS: The peripheral blood samples from 32 patients(21 cases of lymphoma and 11 cases of lymphadenitis) with superficial lymph node enlargement were collected, 9 healthy volunteers were as the normal control...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27781380/hodgkin-lymphoma-hiv-and-epstein-barr-virus-in-malawi-longitudinal-results-from-the-kamuzu-central-hospital-lymphoma-study
#10
Katherine D Westmoreland, Christopher C Stanley, Nathan D Montgomery, Bongani Kaimila, Edwards Kasonkanji, Nader Kim El-Mallawany, Peter Wasswa, Idah Mtete, Mercy Butia, Salama Itimu, Mary Chasela, Mary Mtunda, Maria Chikasema, Victor Makwakwa, Coxcilly Kampani, Bal M Dhungel, Marcia K Sanders, Robert Krysiak, Tamiwe Tomoka, N George Liomba, Dirk P Dittmer, Yuri Fedoriw, Satish Gopal
BACKGROUND: Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. METHODS: We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. RESULTS: Among 31 patients with confirmed cHL, the median age was 19 years (range, 2-51 years) and 22 (71%) were male...
October 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27711974/next-generation-sequencing-based-detection-of-circulating-tumour-dna-after-allogeneic-stem-cell-transplantation-for-lymphoma
#11
Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
December 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27690235/dnmt3a-is-a-haploinsufficient-tumor-suppressor-in-cd8-peripheral-t-cell-lymphoma
#12
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27610206/aberrant-methylation-of-cell-free-circulating-dna-in-plasma-predicts-poor-outcome-in-diffuse-large-b-cell-lymphoma
#13
Lasse Sommer Kristensen, Jakob Werner Hansen, Søren Sommer Kristensen, Dorte Tholstrup, Laurine Bente Schram Harsløf, Ole Birger Pedersen, Peter De Nully Brown, Kirsten Grønbæk
BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients and to evaluate this as a prognostic marker. Furthermore, we wanted to follow possible changes in methylation levels during treatment. Seventy-four patients were enrolled in the study, of which 59 received rituximab and CHOP-like chemotherapy...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27539624/molecular-monitoring-of-cell-free-circulating-tumor-dna-in-non-hodgkin-lymphoma
#14
REVIEW
Christopher Melani, Mark Roschewski
The ability to precisely monitor the effectiveness of therapy for non-Hodgkin lymphoma has important clinical implications. In patients with curable lymphomas, such as diffuse large B-cell lymphoma, the eradication of all disease is necessary for cure. In patients with incurable lymphomas, such as follicular lymphoma and mantle cell lymphoma, deep and durable remissions are associated with improvements in survival. Radiographic imaging modalities such as computed tomography and positron emission tomography are the current gold standard for monitoring therapy, but they are fundamentally limited by radiation risks, costs, lack of tumor specificity, and inability to detect disease at the molecular level...
August 2016: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/27533086/clinical-outcomes-of-advanced-non-small-cell-lung-cancer-patients-with-egfr-mutation-alk-rearrangement-and-egfr-alk-co-alterations
#15
Na-Na Lou, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Li-Xu Yan, Zhi Xie, Jian Su, Zhi-Hong Chen, Hai-Yan Tu, Hong-Hong Yan, Zhen Wang, Chong-Rui Xu, Ben-Yuan Jiang, Bin-Chao Wang, Xiao-Yan Bai, Wen-Zhao Zhong, Yi-Long Wu, Jin-Ji Yang
The co-occurrence of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular subtype of non-small-cell lung cancer (NSCLC). Herein, we assessed the clinical outcomes and incidence of acquired resistance to tyrosine kinase inhibitors (TKIs) in this subtype. So we enrolled 118 advanced NSCLC treated with TKIs. EGFR mutations and ALK rearrangements were detected by DNA sequencing or Scorpion amplification refractory mutation system and fluorescence in situ hybridization respectively...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27521316/increased-levels-of-plasma-epstein-barr-virus-dna-identify-a-poor-risk-subset-of-patients-with-advanced-stage-cutaneous-t-cell-lymphoma
#16
Bradley M Haverkos, Alejandro A Gru, Susan M Geyer, Anissa K Bingman, Jessica A Hemminger, Anjali Mishra, Henry K Wong, Preeti Pancholi, Aharon G Freud, Michael A Caligiuri, Robert A Baiocchi, Pierluigi Porcu
INTRODUCTION: Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein-Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. PATIENTS AND METHODS: Patients (n = 46; 2006-2013) with AS CTCL (≥IIB) were retrospectively studied...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27515251/non-hodgkin-lymphoma-and-pre-existing-conditions-spectrum-clinical-characteristics-and-outcome-in-213-children-and-adolescents
#17
Andishe Attarbaschi, Elisa Carraro, Oussama Abla, Shlomit Barzilai-Birenboim, Simon Bomken, Laurence Brugieres, Eva Bubanska, Birgit Burkhardt, Alan K S Chiang, Monika Csoka, Alina Fedorova, Janez Jazbec, Edita Kabickova, Zdenka Krenova, Jelena Lazic, Jan Loeffen, Georg Mann, Felix Niggli, Natalia Miakova, Tomoo Osumi, Leila Ronceray, Anne Uyttebroeck, Denise Williams, Wilhelm Woessmann, Grazyna Wrobel, Marta Pillon
Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27479820/detection-and-prognostic-value-of-recurrent-exportin-1-mutations-in-tumor-and-cell-free-circulating-dna-of-patients-with-classical-hodgkin-lymphoma
#18
Vincent Camus, Aspasia Stamatoullas, Sylvain Mareschal, Pierre-Julien Viailly, Nasrin Sarafan-Vasseur, Elodie Bohers, Sydney Dubois, Jean Michel Picquenot, Philippe Ruminy, Catherine Maingonnat, Philippe Bertrand, Marie Cornic, Valérie Tallon-Simon, Stéphanie Becker, Liana Veresezan, Thierry Frebourg, Pierre Vera, Christian Bastard, Hervé Tilly, Fabrice Jardin
Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study...
September 2016: Haematologica
https://www.readbyqxmd.com/read/27311286/-latest-treatment-of-viral-hepatitis-overcoming-hepatitis-c-and-reactivation-of-hepatitis-b
#19
REVIEW
Yasuhito Tanaka
Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors...
February 2016: Rinsho Byori. the Japanese Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27203405/double-epigenetic-modulation-of-high-dose-chemotherapy-with-azacitidine-and-vorinostat-for-patients-with-refractory-or-poor-risk-relapsed-lymphoma
#20
Yago Nieto, Benigno C Valdez, Peter F Thall, Roy B Jones, Wei Wei, Alan Myers, Chitra Hosing, Sairah Ahmed, Uday Popat, Elizabeth J Shpall, Muzaffar Qazilbash, Alison Gulbis, Paolo Anderlini, Nina Shah, Qaiser Bashir, Amin Alousi, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Richard Champlin, Borje S Andersson
BACKGROUND: More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill...
September 1, 2016: Cancer
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