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https://www.readbyqxmd.com/read/28106467/follicular-lymphoma-a-b-cell-malignancy-addicted-to-epigenetic-mutations
#1
Koorosh Korfi, Sara Ali, James A Heward, Jude Fitzgibbon
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28105297/follicular-lymphoma-the-management-of-elderly-patient
#2
REVIEW
Alessia Castellino, Elisa Santambrogio, Maura Nicolosi, Barbara Botto, Carola Boccomini, Umberto Vitolo
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, which typically affects mature adults and elderly, whose median age at diagnosis is 65 years. The natural history of FL appears to have been favorably impacted by the introduction of Rituximab. Randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival and new strategies of chemo-immunotherapy, such as Bendamustine combined with Rituximab, showed optimal results on response and reduced hematological toxicity, becoming one of the standard treatments, particularly in elderly patients...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28103725/a-phase-1-study-of-bortezomib-and-romidepsin-in-patients-with-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-indolent-b-cell-lymphoma-peripheral-t-cell-lymphoma-or-cutaneous-t-cell-lymphoma
#3
Beata Holkova, Victor Yazbeck, Maciej Kmieciak, Prithviraj Bose, Shuo Ma, Amy Kimball, Mary Beth Tombes, Ellen Shrader, Wen Wan, Caryn Weir-Wiggins, Amanda Singh, Kevin T Hogan, Sarah Conine, Heidi Sankala, John D Roberts, Thomas C Shea, Steven Grant
A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m(2) bortezomib and 10 mg/m(2) romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease...
January 19, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28095352/the-relationship-of-rel-proto-oncogene-to-pathobiology-and-chemoresistance-in-follicular-and-transformed-follicular-lymphoma
#4
Xiaozhou Hu, Esra Baytak, Jinnan Li, Burcu Akman, Kaan Okay, Genfu Hu, Anna Scuto, Wenyan Zhang, Can Küçük
Follicular lymphoma (FL) is a common type of indolent lymphoma that occasionally transforms to more aggressive B-cell lymphomas. These transformed follicular lymphomas (tFL) are often associated with chemoresistance whose mechanisms are currently unknown. REL, a proto-oncogene located on frequently amplified 2p16.1-p15 locus, promotes tumorigenesis in many cancer types through deregulation of the NF-κB pathway; however, its role in FL pathobiology or chemoresistance has not been addressed. Here, we evaluated REL gene copy number by q-PCR on FFPE FL tumor samples, and observed REL amplification in 30...
January 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28094575/treatment-approaches-of-hard-to-treat-non-hodgkin-lymphomas
#5
Lakshminarayanan Nandagopal, Amitkumar Mehta
Even after recent advancements with monoclonal antibodies, antibody drug conjugates and immune therapies, relapsed and refractory lymphomas remain challenging to treat; and the definition and treatment approaches of hard-to-treat lymphomas (HTL) continue to evolve. Areas covered: In this review, we will address HTL encompassing diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and peripheral T cell lymphomas (PTCL). DLBCL, which comprises 30-40% of non-Hodgkin lymphomas is a highly aggressive and heterogeneous malignancy, with primary refractory or relapsed disease remaining a therapeutic challenge...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28076910/treatment-of-patients-with-waldenstr%C3%A3-m-macroglobulinaemia-clinical-practice-guidelines-from-the-myeloma-foundation-of-australia-medical-and-scientific-advisory-group
#6
Dipti Talaulikar, Constantine S Tam, Douglas Joshua, Joy Phoebe Ho, Jeff Szer, Hang Quach, Andrew Spencer, Simon Harrison, Peter Mollee, Andrew W Roberts, Noemi Horvath, Cindy Lee, Andrew Zannettino, Ross Brown, Bradley Augustson, Wilfrid Jaksic, John Gibson, Anna Kalff, Anna Johnston, Judith Trotman, Akash Kalro, George Grigoriadis, Chris Ward, H Miles Prince
Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM...
January 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28064239/recurrent-somatic-mutations-affecting-b-cell-receptor-signaling-pathway-genes-in-follicular-lymphoma
#7
Kilannin Krysiak, Felicia Gomez, Brian S White, Matthew Matlock, Christopher A Miller, Lee Trani, Catrina C Fronick, Robert S Fulton, Friederike Kreisel, Amanda F Cashen, Kenneth R Carson, Melissa M Berrien-Elliott, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger
Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. In order to improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole exome sequencing was performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data, and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples, from 105 primarily treatment-naïve individuals...
November 14, 2016: Blood
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#8
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28061982/pi3k-signaling-pathway-in-normal-b-cells-and-indolent-b-cell-malignancies
#9
REVIEW
Georgios Pongas, Bruce D Cheson
In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3Kδ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and relapsed follicular lymphoma (FL)...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28055107/results-of-a-phase-i-ii-study-of-fenretinide-and-rituximab-for-patients-with-indolent-b-cell-lymphoma-and-mantle-cell-lymphoma
#10
Andrew J Cowan, Phillip A Stevenson, Ted A Gooley, Shani L Frayo, George R Oliveira, Stephen D Smith, Damian J Green, Jennifer E Roden, John M Pagel, Brent L Wood, Oliver W Press, Ajay K Gopal
Fenretinide, a synthetic retinoid, induces apoptotic cell death in B-cell non-Hodgkin lymphoma (B-NHL) and acts synergistically with rituximab in preclinical models. We report results from a phase I-II study of fenretinide with rituximab for B-NHLs. Eligible diagnoses included indolent B-NHL or mantle cell lymphoma. The phase I design de-escalated from fenretinide at 900 mg/m(2) PO BID for days 1-5 of a 7-day cycle. The phase II portion added 375 mg/m(2) IV rituximab weekly on weeks 5-9 then every 3 months...
January 5, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28040699/recommendations-for-clinical-trial-development-in-follicular-lymphoma
#11
REVIEW
Kami Maddocks, Paul M Barr, Bruce D Cheson, Richard F Little, Lawrence Baizer, Brad S Kahl, John P Leonard, Nathan Fowler, Leo I Gordon, Brian K Link, Jonathan W Friedberg, Stephen M Ansell
Follicular lymphoma (FL) is the second most common lymphoid malignancy, representing 20% to 25% of all cases of non-Hodgkin's lymphoma (NHL), and the most common of the indolent NHLs. FL is considered incurable in the majority of patients with the current standard therapeutic approaches, although outcomes have improved in the last few decades with our current therapies, with a median overall survival that now exceeds 18 years. While the majority of patients with FL have improved outcomes with our current therapeutic approaches, there are patients with high-risk disease features that have inferior outcomes to these therapies...
March 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28038857/similar-prognosis-of-transformed-and-de-novo-diffuse-large-b-cell-lymphomas-in-patients-treated-with-immunochemotherapy
#12
Marc Sorigue, Olga Garcia, Maria Joao Baptista, Juan-Manuel Sancho, Gustavo Tapia, José Luis Mate, Evarist Feliu, José-Tomás Navarro, Josep-Maria Ribera
BACKGROUND: The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. PATIENTS AND METHODS: We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. RESULTS: Patients with TL and de novo DLBCL had similar characteristics...
December 27, 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28035765/risk-stratification-of-adult-t-cell-leukemia-lymphoma-using-immunophenotyping
#13
Huseini H Kagdi, Maria A Demontis, Paul A Fields, Juan Carlos Ramos, Charles R M Bangham, Graham P Taylor
Adult T-cell leukemia/lymphoma (ATL), a human T-lymphotropic virus type 1 (HTLV-1)-associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from 10 HTLV-1-uninfected subjects (UI), 54 HTLV-1-infected patients with non-ATL, and 22 with ATL was performed using flow cytometry...
December 30, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/28029309/thirty-month-complete-response-as-a-surrogate-end-point-in-first-line-follicular-lymphoma-therapy-an-individual-patient-level-analysis-of-multiple-randomized-trials
#14
Qian Shi, Christopher R Flowers, Wolfgang Hiddemann, Robert Marcus, Michael Herold, Anton Hagenbeek, Eva Kimby, Howard Hochster, Umberto Vitolo, Bruce A Peterson, Emmanuel Gyan, Michele Ghielmini, Tina Nielsen, Sabine De Bedout, Tommy Fu, Nancy Valente, Nathan H Fowler, Eva Hoster, Marco Ladetto, Franck Morschhauser, Emanuele Zucca, Gilles Salles, Daniel J Sargent
Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28025783/idelalisib-induced-colitis-and-skin-eruption-mimicking-graft-versus-host-disease
#15
Muhammad Bader Hammami, Ahmad Al-Taee, Marshall Meeks, Mark Fesler, M Yadira Hurley, Dengfeng Cao, Jin-Ping Lai
INTRODUCTION: Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. CASE PRESENTATION: We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib...
December 26, 2016: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28024489/-divergence-analysis-of-hepatitis-virus-infection-between-aggressive-and-indolent-b-cell-non-hodgkin-s-lymphoma
#16
Wen-Jie Xiong, Heng Li, Hui-Min Liu, Shu-Hua Yi, Zeng-Jun Li, Rui Lu, Wei Liu, De-Hui Zou, Lu-Gui Qiu
OBJECTIVE: To investigate the prevalence rate of hepatitis B virus(HBV)and hepatitis C virus(HCV)between aggressive and indolent B cell non-Hodgkin's lymphoma (B-NHL), and to compare the different infection rate of Hepatifis Virus between the 2 groups. METHODS: Integrated clinical information of 733 newly diagnosed indolent B-NHL patients and 148 aggressive B-NHL patients from January 1994 to January 2014 was retrospectively analyzed. The difference of hepatitis virus infection was compared between the 2 groups...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28018857/murine-models-of-splenic-marginal-zone-lymphoma-a-role-for-cav1
#17
REVIEW
Chelsey L Patten, Christine E Cutucache
Dozens of murine models of indolent and aggressive B-cell lymphomas have been generated to date. These include those manifesting chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), as well as xenografts of mantle cell lymphoma (MCL). These models have led to an improved understanding of disease etiology, B-cell biology, immunomodulation, and the importance of the tumor microenvironment. Despite these efforts in CLL, DLBCL, and MCL, considerably little progress toward a model of splenic marginal zone lymphoma (SMZL) has been accomplished...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/28017967/duvelisib-treatment-is-associated-with-altered-expression-of-apoptotic-regulators-that-helps-in-sensitization-of-chronic-lymphocytic-leukemia-cells-to-venetoclax-abt-199
#18
V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda, S O'Brien, N Jain, H M Stern, V Gandhi
Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28004361/a-review-of-obinutuzumab-ga101-a-novel-type-ii-anti-cd20-monoclonal-antibody-for-the-treatment-of-patients-with-b-cell-malignancies
#19
REVIEW
Kensei Tobinai, Christian Klein, Naoko Oya, Günter Fingerle-Rowson
Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies...
December 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27998446/-preliminary-evaluation-of-pet-ct-and-dwi-for-the-detection-of-lymphoma-bone-marrow-infiltration
#20
Y Wu, L P Su, X T Yang, J X Zhang, M Zhao, Z Zhang, T Guan, X L Liu, Y P Zheng, W E Han
Objective: To evaluate the clinical value of PET-CT and DWI for the detection of bone marrow infiltration of lymphoma. Methods: The bone marrow samples of 93 untreated patients with pathologically diagnosed lymphoma were retrospectively analyzed. 61 patients underwent PET-CT examination, and other 32 underwent DWI examination. With bone marrow biopsy results as "gold standard" , the rates and sites of bone marrow infiltration of various lymphoma subtypes were analyzed, and the detection rates of the two imaging techniques were compared according to different lymphoma subtypes...
November 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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