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Adult large T cell Lymphoma

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https://www.readbyqxmd.com/read/30528964/recent-advances-in-car-t-cell-toxicity-mechanisms-manifestations-and-management
#1
REVIEW
Jennifer N Brudno, James N Kochenderfer
Chimeric antigen receptor (CAR) T-cell therapy is an effective new treatment for hematologic malignancies. Two CAR T-cell products are now approved for clinical use by the U.S. FDA: tisagenlecleucel for pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma subtypes (DLBCL), and axicabtagene ciloleucel for DLBCL. CAR T-cell therapies are being developed for multiple myeloma, and clear evidence of clinical activity has been generated. A barrier to widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) and neurologic toxicity...
November 14, 2018: Blood Reviews
https://www.readbyqxmd.com/read/30522922/brentuximab-vedotin-with-chemotherapy-for-cd30-positive-peripheral-t-cell-lymphoma-echelon-2-a-global-double-blind-randomised-phase-3-trial
#2
Steven Horwitz, Owen A O'Connor, Barbara Pro, Tim Illidge, Michelle Fanale, Ranjana Advani, Nancy L Bartlett, Jacob Haaber Christensen, Franck Morschhauser, Eva Domingo-Domenech, Giuseppe Rossi, Won Seog Kim, Tatyana Feldman, Anne Lennard, David Belada, Árpád Illés, Kensei Tobinai, Kunihiro Tsukasaki, Su-Peng Yeh, Andrei Shustov, Andreas Hüttmann, Kerry J Savage, Sam Yuen, Swaminathan Iyer, Pier Luigi Zinzani, Zhaowei Hua, Meredith Little, Shangbang Rao, Joseph Woolery, Thomas Manley, Lorenz Trümper
BACKGROUND: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. METHODS: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study...
December 3, 2018: Lancet
https://www.readbyqxmd.com/read/30511461/survival-after-diffuse-large-b-cell-lymphoma-among-children-adolescents-and-young-adults-in-california-2001-2014-a-population-based-study
#3
R Abrahão, R C Ribeiro, D Y Lichtensztajn, A S Rosenberg, T H M Keegan
BACKGROUND: This population-based study considered the influence of rituximab on the survival of children (0-19 years), adolescents, and young adults (AYAs, 20-39 years) with diffuse large B-cell lymphoma (DLBCL), including patients with human immunodeficiency virus (HIV) infection. METHODS: Data on 642 children and AYAs diagnosed with DLBCL during 2001-2014 were obtained from the Greater Bay Area Cancer Registry in California. Facility-level reports provided treatment details...
December 4, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/30501490/tisagenlecleucel-in-adult-relapsed-or-refractory-diffuse-large-b-cell-lymphoma
#4
Stephen J Schuster, Michael R Bishop, Constantine S Tam, Edmund K Waller, Peter Borchmann, Joseph P McGuirk, Ulrich Jäger, Samantha Jaglowski, Charalambos Andreadis, Jason R Westin, Isabelle Fleury, Veronika Bachanova, S Ronan Foley, P Joy Ho, Stephan Mielke, John M Magenau, Harald Holte, Serafino Pantano, Lida B Pacaud, Rakesh Awasthi, Jufen Chu, Özlem Anak, Gilles Salles, Richard T Maziarz
BACKGROUND: Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation...
December 1, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/30385085/clinical-and-histopathological-significance-of-pd-1-expression-in-cutaneous-lesions-of-adult-t-cell-leukemia-lymphoma
#5
Maho Higuchi, Yutaka Kuwatsuka, Hiroyuki Murota, Masako Iwanaga, Daisuke Niino
BACKGROUND: Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection and is known to exhibit cutaneous involvement in 50% or more patients. Few studies have evaluated the clinicopathological significance of programmed death-1 (PD-1) expression in the cutaneous lesions of ATL. METHODS: Skin biopsy specimens from 29 ATL patients with cutaneous lesions were evaluated regarding the clinicopathological feature, survival outcome, and PD-1 expression level on infilitrated CD3+CD4 + CD25+ cells...
October 21, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/30368656/epstein-barr-virus-related-diffuse-large-b-cell-lymphoma-in-mogamulizumab-treated-adult-t-cell-leukemia-with-incomplete-t-cell-reconstitution
#6
Kazuharu Kamachi, Takero Shindo, Masaharu Miyahara, Kazutaka Kitaura, Michiaki Akashi, Tadasu Shin-I, Ryuji Suzuki, Koichi Oshima, Shinya Kimura
Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C-C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein-Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system...
October 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/30333224/cerdulatinib-pharmacodynamics-and-relationships-to-tumor-response-following-oral-dosing-in-patients-with-relapsed-refractory-b-cell-malignancies
#7
Greg P Coffey, Greg P Coffey, Andreas Betz, Jiajia Feng, Anjali Pandey, Matt Birrell, Janet M Leeds, Kenneth Der, Sabah Kadri, Pin Lu, Jeremy P Segal, Y Lynn Wang, Glenn Michelson, John T Curnutte, Pamela B Conley
PURPOSE: Preclinical studies suggest SYK and JAK contribute to tumor intrinsic and microenvironment-derived survival signals. The pharmacodynamics of cerdulatinib, a dual SYK/JAK inhibitor, and associations with tumor response were investigated. EXPERIMENTAL DESIGN: In a phase I dose-escalation study in adults with relapsed/refractory B-cell malignancies, cerdulatinib was administered orally to sequential dose-escalation cohorts using once-daily or twice-daily schedules...
October 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30327177/what-s-in-a-name-the-heterogeneous-clinical-spectrum-and-prognostic-factors-in-a-cohort-of-adults-with-hemophagocytic-lymphohistiocytosis
#8
Bonnie C Prokesch, Srikanth Nagalla, Fatemeh Ezzati, Shannan R Tujios, Arturo Dominguez, Weina Chen, Corey Kershaw, Prapti Patel, Carolina de la Flor, Jeannine Foster, Andrew A Martin, Maria Teresa de la Morena, Christian A Wysocki
PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) in adults is rare but frequently fatal. Diagnosis is often delayed and treatment approaches vary significantly in contrast to the protocol-driven approach typically used in pediatric HLH. To improve care of these complex patients, this study retrospectively examined the prevalence, clinical characteristics, therapies and outcomes of adult HLH patients at two large tertiary care centers. METHODS: Adult patients with HLH confirmed by retrospective review of electronic medical records using HLH2004 criteria during admissions to the University of Texas Southwestern and Parkland Memorial Hospitals between June 2007 and June 2017 were studied...
October 6, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/30319719/-ewsr1-rearrangement-and-cd99-expression-as-diagnostic-biomarkers-for-ewing-pnet-sarcomas-in-a-moroccan-population
#9
Sara Louati, Nadia Senhaji, Laila Chbani, Sanae Bennis
Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) are a group of round cell tumors. Malignant round cell tumors form a large and diverse group that includes rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, neuroblastoma, hepatoblastoma, Wilm's tumor, desmoplastic small round cell tumor, and other morphologically similar entities. Differential diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) is difficult. In addition to morphology and immunohistochemistry (IHC), differential diagnosis of these tumors is based on molecular analysis of the EWSR1 gene rearrangement using fluorescent in situ hybridization (FISH) technique...
2018: Disease Markers
https://www.readbyqxmd.com/read/30303535/decreased-rorc-expression-and-downstream-signaling-in-htlv-1-associated-adult-t-cell-lymphoma-leukemia-uncovers-an-antiproliferative-il17-link-a-potential-target-for-immunotherapy
#10
Kritika Subramanian, Tim Dierckx, Ricardo Khouri, Soraya Maria Menezes, Huseini Kagdi, Graham P Taylor, Lourdes Farre, Achilea Bittencourt, Keisuke Kataoka, Seishi Ogawa, Johan Van Weyenbergh
Retinoic acid-related drugs have shown promising pre-clinical activity in Adult T-cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we investigated transcriptome-wide interactions of the RORC pathway in HTLV-1 and ATL, using our own and publicly available gene expression data for ATL and other leukemias. Gene expression data from ATL patients were analyzed using WGCNA to determine gene modules and their correlation to clinical and molecular data. Both PBMCs and CD4+ T-cells showed decreased RORC expression in four different ATL cohorts...
October 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30260711/cost-effectiveness-of-axicabtagene-ciloleucel-for-adult-patients-with-relapsed-or-refractory-large-b-cell-lymphoma-in-the-united-states
#11
Joshua A Roth, Sean D Sullivan, Vincent W Lin, Aasthaa Bansal, Anna G Purdum, Lynn Navale, Paul Cheng, Scott D Ramsey
PURPOSE: Axicabtagene ciloleucel (axi-cel) was recently approved for treatment of relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following two or more prior therapies. As the first CAR T-cell therapy available for adults in the US, there are important questions about clinical and economic value. The objective of this study was to assess the cost-effectiveness of axi-cel compared to salvage chemotherapy using a decision model and a US payer perspective. MATERIALS AND METHODS: A decision model was developed to estimate life years (LYs), quality-adjusted life years (QALYs), and lifetime cost for adult patients with R/R LBCL treated with axi-cel vs salvage chemotherapy (R-DHAP)...
December 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/30218163/intensive-care-unit-admission-in-patients-with-t-cell-lymphomas-clinical-features-and-outcome
#12
Guillaume Dumas, Lucie Biard, Claire Givel, Sandy Amorim, Lara Zafrani, Virginie Lemiale, Eric Mariotte, Elie Azoulay, Catherine Thiéblemont, Emmanuel Canet
T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a high risk of life-threatening complications. However, their prognosis in the intensive care unit (ICU) setting has not yet been assessed. We conducted a study including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing first-line therapy admitted between January 1, 2000, and December 31, 2014. The primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL) (n = 11, 13%)...
September 14, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/30153323/peripheral-t-cell-lymphomas-incorporating-new-developments-in-diagnostics-prognostication-and-treatment-into-clinical-practice-part-2-enktl-eatl-indolent-t-cell-ldp-of-the-gi-tract-atll-and-hepatosplenic-t-cell-lymphoma
#13
REVIEW
Natalia Pin Chuen Zing, Thais Fischer, Jasmine Zain, Massimo Federico, Steven T Rosen
The World Health Organization classification for peripheral T-cell lymphomas (PTCLs) continues to evolve based on genetic and clinical distinctions of each entity. In Part 1, an overview was provided of PTCL not otherwise specified, follicular T-cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma (ALCL), and breast implant-associated ALCL. In Part 2, this review is extended to extranodal natural killer (NK)/T-cell lymphoma, enteropathy-associated T-cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, adult T-cell leukemia/lymphoma, and hepatosplenic T-cell lymphoma...
August 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/30138509/human-t-lymphotropic-virus-1-associated-with-adult-t-cell-leukemia-lymphoma
#14
Travis James, David Fivenson, Jenny Cotton
Adult T-cell leukemia/lymphoma (ATLL) is an uncommon neoplasm of mature T lymphocytes associated with infection by human T-lymphotropic virus 1 (HTLV-1), which is increasing in incidence in areas of the United States with large immigrant populations. Human T-lymphotrophic virus 1 infection is asymptomatic in most patients and has been associated with ATLL as well as tropical spastic paraparesis. Because there is considerable histologic overlap with other cutaneous T-cell lymphomas, high suspicion and clinical features must be present to make the diagnosis of ATLL...
July 2018: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/30127547/management-of-lymphomas-consensus-document-2018-by-an-indian-expert-group
#15
REVIEW
Reena Nair, Abhishek Kakroo, Ajay Bapna, Ajay Gogia, Amish Vora, Anand Pathak, Anu Korula, Anupam Chakrapani, Dinesh Doval, Gaurav Prakash, Ghanashyam Biswas, Hari Menon, Maitreyee Bhattacharya, Mammen Chandy, Mayur Parihar, M Vamshi Krishna, Neeraj Arora, Nikhil Gadhyalpatil, Pankaj Malhotra, Prasad Narayanan, Rekha Nair, Rimpa Basu, Sandip Shah, Saurabh Bhave, Shailesh Bondarde, Shilpa Bhartiya, Soniya Nityanand, Sumeet Gujral, T V S Tilak, Vivek Radhakrishnan
The clinical course of lymphoma depends on the indolent or aggressive nature of the disease. Hence, the optimal management of lymphoma needs a correct diagnosis and classification as B cell, T-cell or natural killer (NK)/T-cell as well as indolent or high-grade type lymphoma. The current consensus statement, developed by experts in the field across India, is intended to help healthcare professionals manage lymphomas in adults over 18 years of age. However, it should be noted that the information provided may not be appropriate to all patients and individual patient circumstances may dictate alternative approaches...
July 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/30124892/appropriate-radiation-dose-for-symptomatic-relief-and-local-control-in-patients-with-adult-t-cell-leukemia-lymphoma
#16
Hitoshi Maemoto, Takuro Ariga, Sawako Nakachi, Takafumi Toita, Seiji Hashimoto, Joichi Heianna, Hideki Shiina, Takeaki Kusada, Wataru Makino, Yasumasa Kakinohana, Takuya Miyagi, Yuichi Yamamoto, Satoko Morishima, Hiroaki Masuzaki, Sadayuki Murayama
Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm that occurs only in patients with human T-cell leukemia virus type 1. No large study or randomized trial investigating radiotherapy (RT) for ATL has been performed. We retrospectively reviewed 55 courses of RT for 41 consecutive patients with ATL who underwent RT between 2000 and 2016 at our institutions. The results showed that RT for local ATL lesions can achieve symptomatic improvement in 92% of cases. Local remission, either complete remission (CR) or partial response (PR), was achieved in 100% of the patients (CR: 89%, PR: 11%) with ≥40 Gy irradiation...
August 17, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/30120708/car-t-cell-therapy-for-acute-lymphoblastic-leukemia-transforming-the-treatment-of-relapsed-and-refractory-disease
#17
REVIEW
Katherine C Pehlivan, Brynn B Duncan, Daniel W Lee
PURPOSE OF REVIEW: Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy. RECENT FINDINGS: CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting...
October 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/30117170/extranodal-lymphomas-in-the-public-health-system-in-chile-analysis-of-1251-patients-from-the-national-adult-cancer-program
#18
Camila Peña, Moises Russo, Virginia Martinez, Maria Elena Cabrera
The aim of the study was to describe the clinical and epidemiological characteristics, anatomic and histologic distribution, and treatment results of extranodal lymphomas (ENLs), diagnosed and treated in the public health system in Chile. We included patients with ENL diagnosed from 1998 to 2014, in 17 cancer centers, registered prospectively in the database of the National Adult Cancer Program (PANDA) of the Ministry of Health. Treatment was based on the local protocols for each lymphoma subtype. Extranodal lymphoma was documented in 1215 of 4907 non-Hodgkin lymphomas diagnosed in that period (25%)...
August 16, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/30082570/peripheral-t-cell-lymphoma-clinico-pathological-characteristics-outcome-from-a-tertiary-care-centre-in-south-india
#19
Sandeep Nemani, Anu Korula, Bhumi Agrawal, M L Kavitha, Marie Therese Manipadam, Elanthenral Sigamani, Biju George, Alok Srivastava, Auro Viswabandya, Vikram Mathews
Background & objectives: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin's lymphomas (NHLs), with universally poor outcome. This study was undertaken to provide data on demographics and outcomes of patients with PTCL who underwent treatment in a single tertiary care centre in southern India. Methods: Retrospective study was done on all patients (age ≥18 yr) diagnosed with PTCL from January 2007 to December 2012. The diagnosis of PTCL was made according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues...
May 2018: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/30080923/peripheral-t-cell-lymphomas-incorporating-new-developments-in-diagnostics-prognostication-and-treatment-into-clinical-practice-part-1-ptcl-nos-ftcl-aitl-alcl
#20
REVIEW
Natalia Pin Chuen Zing, Thais Fischer, Jasmine Zain, Massimo Federico, Steven T Rosen
Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of diseases, with low incidence and unique epidemiology and pathobiology; they are usually clinically aggressive, with poor outcomes. There have been significant advances in our understanding of the molecular and signaling alterations seen in these malignancies. These observations have led to novel therapeutic strategies that have had a meaningful impact on outcomes. This two-part series highlights the most important aspects of PTCLs and describes current treatment options and investigative opportunities...
July 15, 2018: Oncology (Williston Park, NY)
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