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Double-Hit Lymphoma

M Kopáčková, P Beránek, I Bydžovská, R Pytlík, J Soukup, M Mrhalová
OBJECTIVE: Presentation of a rare finding non-Hodgkin´s B-lymphoma of the ovary in a patient during caesarean section. DESIGN: Case report. SETTINGS: Department of Obstetrics and Gynaecology, Regional Hospital Liberec, a.s.; First Internal Clinic - Clinic of Hematology, First Faculty of Medicine and General University Hospital, Charles University in Prague; Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Praque and Motol University Hospital...
2018: Ceská Gynekologie
Christie Hancock, Phillip Knouse, Imad Almanaseer, Jacob Bitran
BACKGROUND: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies...
February 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
Dongfeng Zeng, Aakash Desai, Fangfang Yan, Tiejun Gong, Haige Ye, Makhdum Ahmed, Krystle Nomie, Jorge Romaguera, Richard Champlin, Shaoying Li, Michael Wang
The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL)...
February 6, 2018: American Journal of Clinical Oncology
Wei Liu, Juan Chen, Archito T Tamayo, Changgeng Ruan, Li Li, Shouhao Zhou, Chan Shen, Ken H Young, Jason Westin, Richard E Davis, Shimin Hu, Leonard J Medeiros, Richard J Ford, Lan V Pham
Despite advances in deciphering the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), patients with relapsed/refractory disease, particularly those with adverse genetic features (e.g., mutated p53 or double hit lymphoma (DHL)) have very poor prognoses, and effective therapies are lacking. In this study we examined the preclinical efficacy and associated biological effects of the first oral proteasome inhibitor, ixazomib, in DLBCL in vitro and in vivo models. We demonstrated that ixazomib exhibited anti-tumor activities in 28 representative DLBCL cell lines, 10 primary DLBCL samples, and a DHL xenotransplant mouse model, at clinically achievable drug concentrations...
January 2, 2018: Oncotarget
Micol Ravà, Aleco D'Andrea, Paola Nicoli, Ilaria Gritti, Giulio Donati, Mirko Doni, Marco Giorgio, Daniela Olivero, Bruno Amati
High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provides a therapeutic window in a mouse model of MYC -driven lymphoma. We now addressed the utility of this antibiotic for treatment of DHL. BCL2 activation in mouse Eμ- myc lymphomas antagonized tigecycline-induced cell death, which was specifically restored by combined treatment with the BCL2 inhibitor venetoclax...
January 31, 2018: Science Translational Medicine
Reem Karmali, Vineela Chukkapalli, Leo I Gordon, Jeffrey A Borgia, Andrey Ugolkov, Andrew P Mazar, Francis J Giles
The complexities of GSK-3β function and interactions with PI3K/AKT/mTOR signaling, cell cycling, and apoptotic pathways are poorly understood in the context of lymphomagenesis and cancer therapeutics. In this study, we explored the anti-tumor effects of the GSK-3β inhibitor, 9-ING-41, in lymphoma cell lines as a single agent and in combination with novel agents comprising BCL-2 inhibitor (Venetoclax), CDK-9 inhibitor (BAY-1143572) and p110δ-PI3K inhibitor (Idelalisib). Treatment of Daudi, SUDHL-4, Karpas 422, KPUM-UH1, and TMD8 lymphoma cell lines with 1 μM 9-ING-41 reduced cell viability by 40-70% (p<0...
December 29, 2017: Oncotarget
Carlos Murga-Zamalloa, Avery Polk, Walter Hanel, Pinki Chowdhury, Noah Brown, Alexandra C Hristov, Nathanael G Bailey, Tianjiao Wang, Tycel Phillips, Sumana Devata, Pradeep Poonnen, Juan Gomez-Gelvez, Kedar V Inamdar, Ryan A Wilcox
Survival following anthracycline-based chemotherapy remains poor among patients with most T-cell lymphoproliferative disorders. This may be attributed, at least in part, to cell-autonomous mechanisms of chemotherapy resistance observed in these lymphomas, including the loss of important tumor suppressors and the activation of signaling cascades that culminate in the expression and activation of transcription factors promoting cell growth and survival. Therefore, the identification of novel therapeutic targets is needed...
December 29, 2017: Oncotarget
Diego Villa, Laurie H Sehn
No abstract text is available yet for this article.
January 25, 2018: Leukemia & Lymphoma
A Esteve-Arenys, J G Valero, A Chamorro-Jorganes, D Gonzalez, V Rodriguez, I Dlouhy, I Salaverria, E Campo, D Colomer, A Martinez, G Rymkiewicz, P Pérez-Galán, A Lopez-Guillermo, G Roué
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, mostly known as double-hit lymphoma (DHL), is a rare entity characterized by morphologic and molecular features between Burkitt lymphoma and the clinically manageable diffuse large B-cell lymphoma (DLBCL). DHL patients usually undergo a rapidly progressing clinical course associated with resistance to standard chemo-immunotherapy. As a consequence, the prognosis of this entity is particularly poor with a median overall survival inferior to 1 year...
January 22, 2018: Oncogene
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
Michael Scordo
No abstract text is available yet for this article.
January 12, 2018: Biology of Blood and Marrow Transplantation
W J Yin, X Zhu, H Y Yang, W Y Sun, M J Wu
Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER)...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Daisuke Minakata, Kazuya Sato, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Iekuni Oh, Shin-Ichiro Fujiwara, Ken Ohmine, Hirotoshi Kawata, Kazuo Muroi, Ikuo Miura, Yoshinobu Kanda
Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes...
January 2018: Cancer Genetics
L K Schoch, A Asiama, M Zahurak, S Shanbhag, J Hurtt, K Sawyer, L J Swinnen, N Wagner-Johnston, R J Jones, R F Ambinder, Douglas E Gladstone
BACKGROUND: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients. PATIENTS/METHODS: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities...
December 13, 2017: Cancer Chemotherapy and Pharmacology
Patrick M Reagan, Andrew Davies
A 60-year-old female presented with abdominal pain and distension. Following computed tomography scans of the abdomen and pelvis, she was taken urgently to the operating room, with the belief that she had appendicitis with perforation. At laparotomy, the findings were consistent with an ovarian carcinoma; there was extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive surgery was performed including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The final pathology, however, revealed infiltration with medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6 by immunohistochemistry...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Andrew Davies
Although there have been significant insights into the biology of diffuse large B-cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has been disappointing over the same timeframe. This is not for want of trying. In 2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the "gold standard," despite all of our insights into cell-of-origin and other subgroups. We have traditionally used clinical risk factors to tailor our therapies and have tested intensification of chemotherapy with little success...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Andy I Chen, Jessica T Leonard, Craig Y Okada, Nathan D Gay, Kari Chansky, Guang Fan, Jennifer B Dunlap, Philipp W Raess, Rita M Braziel, Alex Stentz, Richard T Maziarz
High-grade B cell lymphoma with MYC and BCL2 rearrangements (double hit) has a poor prognosis with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). We report here a treatment algorithm of DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) followed by BEAM (carmustine, etoposide, cytarabine, melphalan) autologous transplant in 36 cases of previously untreated double hit lymphoma (DHL) from 2010 to 2015. A high risk International Prognostic Index (IPI) was present in 42% of cases...
December 3, 2017: Leukemia & Lymphoma
Alex F Herrera, Scott J Rodig, Joo Y Song, Young Kim, Gabriel K Griffin, Dongyun Yang, Liana Nikolaenko, Matthew Mei, Victoria Bedell, Paola Dal Cin, Christine Pak, Edwin P Alyea, Lihua E Budde, Robert Chen, Yi-Bin Chen, Wing C Chan, Corey S Cutler, Vincent T Ho, John Koreth, Amrita Krishnan, Joyce L Murata-Collins, Sarah Nikiforow, Joycelynne Palmer, German A Pihan, Raju Pillai, Leslie Popplewell, Steven T Rosen, Tanya Siddiqi, Aliyah R Sohani, Jasmine Zain, Larry W Kwak, Dennis D Weisenburger, David M Weinstock, Robert J Soiffer, Joseph H Antin, Stephen J Forman, Auayporn P Nademanee, Philippe Armand
Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are associated with resistance to frontline and salvage immunochemotherapy, as well as autologous stem cell transplantation (SCT). We hypothesized that allogeneic SCT (alloSCT) could overcome the chemoresistance associated with DEL/DHL. We retrospectively studied the impact of DEL/DHL status in a multicenter cohort of patients who underwent alloSCT for relapsed/refractory (rel/ref) aggressive B cell non-Hodgkin lymphoma (B-NHL). Seventy-eight patients transplanted at 3 centers in whom tumor tissue was available for immunohistochemistry and fluorescence in situ hybridization were enrolled; 47% had DEL and 13% had DHL...
March 2018: Biology of Blood and Marrow Transplantation
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
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