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Adult large T cell Lymphoma

Christopher T Petersen, Giedre Krenciute
High grade gliomas (HGG) comprise a heterogeneous group of brain malignancies with dismal prognosis. Current standard-of-care includes radiation, chemotherapy, and surgical resection when possible. Despite advances in each of these treatment modalities, survival rates for pediatric and adult HGG patients has remained largely unchanged over the course of several years. This is in stark contrast to the significant survival increases seen recently for a variety of hematological and other solid malignancies. The introduction and widespread use of immunotherapies have contributed significantly to these survival increases, and as such these therapies have been explored for use in the treatment of HGG...
2019: Frontiers in Oncology
Elaine Y L Chung, Yun Mai, Urvi A Shah, Yongqiang Wei, Elise Ishida, Keisuke Kataoka, Xiaoxin Ren, Kith Pradhan, Boris Bartholdy, Xiaolei Wei, Yiyu Zou, Jinghang Zhang, Seishi Ogawa, Ulrich Steidl, Xingxing Zang, Amit Verma, Murali Janakiram, Bihui Hilda Ye
PURPOSE: To evaluate therapeutic activity of PAK inhibition in ATLL and to characterize the role of PAK isoforms in cell proliferation, survival, and adhesion of ATLL cells in preclinical models. EXPERIMENTAL DESIGN: Frequency and prognostic impact of PAK2 amplification were evaluated in an ATLL cohort of 370 cases. Novel long term cultures and in vivo xenograft models were developed using primary ATLL cells from North American patients. Two PAK inhibitors were used to block PAK kinase activity pharmacologically...
March 12, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Diego Adrianzen Herrera, Noah Kornblum, Ana Acuna-Villaorduna, R Alejandro Sica, Urvi Shah, Moya Butler, Nivetha Vishnuvardhan, Nishi Shah, Lizamarie Bachier-Rodriguez, Olga Derman, Aditi Shastri, Ioannis Mantzaris, Amit K Verma, Ira Braunchweig, Murali Janakiram
In the United States (U.S.), Adult T-Cell Lymphoma-Leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from Human T-Cell Lymphotropic Virus 1 (HTLV-1) endemic areas. Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the NCCN guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the U.S. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018...
February 12, 2019: Biology of Blood and Marrow Transplantation
Peter Dreger, Anna Sureda, Kwang Woo Ahn, Mary Eapen, Carlos Litovich, Herve Finel, Ariane Boumendil, Ajay Gopal, Alex F Herrera, Christoph Schmid, José Luis Diez-Martin, Ephraim Fuchs, Javier Bolaños-Meade, Mahasweta Gooptu, Monzr M Al Malki, Luca Castagna, Stefan O Ciurea, Alida Dominietto, Didier Blaise, Fabio Ciceri, Johanna Tischer, Paolo Corradini, Silvia Montoto, Stephen Robinson, Zafer Gülbas, Mehdi Hamadani
This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included...
February 12, 2019: Blood Advances
Hirotoshi Maruo, Hajime Tsuyuki, Yuji Shimizu, Yasushi Shibasaki, Koichi Nakamura, Yukihiro Higashi, Tsuyoshi Shoji, Kazuhisa Hirayama, Masanori Yamazaki
We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Hugo Larose, G A Amos Burke, Eric J Lowe, Suzanne D Turner
Anaplastic large cell lymphoma (ALCL) is a T cell Non-Hodgkin Lymphoma that mainly presents in paediatric and young adult patients. The majority of cases express a chimeric fusion protein resulting in hyperactivation of anaplastic lymphoma kinase (ALK) as the consequence of a chromosomal translocation. Rarer cases lack expression of ALK fusion proteins and are categorised as ALCL, ALK-. An adapted regimen of an historic chemotherapy backbone is still used to this day, yielding overall survival (OS) of over 90% but with event-free survival (EFS) at an unacceptable 70%, improving little over the past 30 years...
January 25, 2019: British Journal of Haematology
Stacie Ittershagen, Solveig Ericson, Lamis Eldjerou, Ali Shojaee, Eric Bleickardt, Manisha Patel, Tetiana Taran, Oezlem Anak, Charlene Hall, Mimi Leung, Deborah Roccoberton, Florence Salmon, Miriam Fuchs, Vadim Romanov, David Lebwohl
PURPOSE OF REVIEW: We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children's Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland). RECENT FINDINGS: Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma...
January 21, 2019: Current Hematologic Malignancy Reports
Lucy B Cook, Shigeo Fuji, Olivier Hermine, Ali Bazarbachi, Juan Carlos Ramos, Lee Ratner, Steve Horwitz, Paul Fields, Alina Tanase, Horia Bumbea, Kate Cwynarski, Graham Taylor, Thomas A Waldmann, Achilea Bittencourt, Ambroise Marcais, Felipe Suarez, David Sibon, Adrienne Phillips, Matthew Lunning, Reza Farid, Yoshitaka Imaizumi, Ilseung Choi, Takashi Ishida, Kenji Ishitsuka, Takuya Fukushima, Kaoru Uchimaru, Akifumi Takaori-Kondo, Yoshiki Tokura, Atae Utsunomiya, Masao Matsuoka, Kunihiro Tsukasaki, Toshiki Watanabe
PURPOSE: Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by chronic infection with human T-lymphotropic virus type 1 with diverse clinical features and prognosis. ATL remains a challenging disease as a result of its diverse clinical features, multidrug resistance of malignant cells, frequent large tumor burden, hypercalcemia, and/or frequent opportunistic infection. In 2009, we published a consensus report to define prognostic factors, clinical subclassifications, treatment strategies, and response criteria...
January 18, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Y P Chen, Z J Wu, W Liu, J P Lu, J C Wang, W F Zhu, F F Chen, L H Zhong, G Chen
Objective: To investigate the clinical presentation, clinicopathologic features, diagnosis and differential diagnosis of adult T cell leukemia/lymphoma (ATLL). Methods: Four cases of ATLL from Fujian Cancer Hospital between October 2017 and May 2018 were analyzed using hematoxylin-eosin and immunohistochemical stains and polymerase chain reaction (PCR) for HTLV-1 provirus genes. The relevant literature was reviewed. Results: There were two males and two females, age range 38-80 years. All patients were from coastal cities of Fujian province...
January 8, 2019: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Dai Chihara, Yasuhiro Oki, Michelle A Fanale, Jason R Westin, Loretta J Nastoupil, Sattva Neelapu, Luis Fayad, Nathan H Fowler, Chan Yoon Cheah
Stage I non-Hodgkin lymphoma (NHL) is rare; prognostic impact of different histologic subtypes and treatment modality is still unclear. We used the Surveillance, Epidemiology and End Results (SEER) database to evaluate survival outcomes among adult patients (age ≥ 18 years, N = 58,230) diagnosed with stage I NHL of various histologic subtypes between 1998 and 2014. Five-year disease-specific survival of patients with stage I diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), and peripheral T cell lymphoma (PTCL) was 82%, 92%, 95%, 89%, 78%, 77%, and 77%, respectively...
January 8, 2019: Annals of Hematology
James N Gerson, Elizabeth Handorf, Diego Villa, Alina S Gerrie, Parv Chapani, Shaoying Li, L Jeffrey Medeiros, Michael I Wang, Jonathon B Cohen, Oscar Calzada, Michael C Churnetski, Brian T Hill, Yazeed Sawalha, Francisco J Hernandez-Ilizaliturri, Shalin Kothari, Julie M Vose, Martin A Bast, Timothy S Fenske, Swapna Narayana Rao Gari, Kami J Maddocks, David Bond, Veronika Bachanova, Bhaskar Kolla, Julio Chavez, Bijal Shah, Frederick Lansigan, Timothy F Burns, Alexandra M Donovan, Nina Wagner-Johnston, Marcus Messmer, Amitkumar Mehta, Jennifer K Anderson, Nishitha Reddy, Alexandra E Kovach, Daniel J Landsburg, Martha Glenn, David J Inwards, Reem Karmali, Jason B Kaplan, Paolo F Caimi, Saurabh Rajguru, Andrew Evens, Andreas Klein, Elvira Umyarova, Bhargavi Pulluri, Jennifer E Amengual, Jennifer K Lue, Catherine Diefenbach, Richard I Fisher, Stefan K Barta
PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015...
January 7, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
J Chen, V Mehraj, J Szabo, B Routy, R P Michel, J P Routy
Primary effusion lymphoma (pel) is a rare human herpesvirus 8 (hhv8)-related large B cell lymphoma with plasmablastic, immunoblastic, or anaplastic features that often carries a poor prognosis. This lymphoma occurs mainly in patients with hiv infection, most often with Epstein-Barr virus (ebv) co-infection, and usually presents as body cavity effusions or, less commonly, as extracavitary lesions without effusion (ec-pel). Chemotherapeutic treatment options are limited and require concurrent antiretroviral therapy (art)...
December 2018: Current Oncology
Daniel W Lee, Bianca D Santomasso, Frederick L Locke, Armin Ghobadi, Cameron J Turtle, Jennifer N Brudno, Marcela V Maus, Jae H Park, Elena Mead, Steven Pavletic, William Y Go, Lamis Eldjerou, Rebecca A Gardner, Noelle Frey, Kevin J Curran, Karl Peggs, Marcelo Pasquini, John F DiPersio, Marcel R M van den Brink, Krishna V Komanduri, Stephan A Grupp, Sattva S Neelapu
Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematological malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment of patients with relapsed or refractory B-cell acute lymphoblastic leukemia up to the age of 25 years and/or adults with large B-cell lymphoma. Many more CAR T products as well as other immunotherapies including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells are in clinical development for both hematologic and solid tumor malignancies...
December 25, 2018: Biology of Blood and Marrow Transplantation
Cynthia M Magro, Luke C Olson, Shabnam Momtahen
T cell lymphoproliferative disorders that arise in the skin are mainly derived from post thymic T cells most commonly of CD4 subset. Human CD4 positive T cells are dynamic exhibiting phenotypic and functional malleability. For example, with repetitive antigen exposure most commonly associated with age, CD4 positive T cells acquire a cytotoxic phenotype. The authors present four cases characterized by cutaneous infiltrates of cytotoxic CD30 negative CD4 positive T cells in the skin; three cases were forms of malignant lymphoma other than mycosis fungoides and one case was a reactive lymphomatoid photodermatosis associated with underlying collagen vascular disease...
October 27, 2018: Annals of Diagnostic Pathology
Bhagirathbhai R Dholaria, Christina A Bachmeier, Frederick Locke
Chimeric antigen receptor T-cell (CAR-T) therapy has proven to be a very effective cancer immunotherapy. Axicabtagene ciloleucel and tisagenlecleucel are the first-in-class anti-CD19 CAR-T currently available for relapsed/refractory adult large B-cell lymphoma. Tisagenlecleucel is also available for pediatric and young adult (up to age 25 years) patients with relapsed/refractory B-acute lymphoblastic leukemia. Cytokine release syndrome (CRS) and CAR-T-associated encephalopathy syndrome (neurotoxicity) are the most common adverse effects associated with CAR-T therapy...
December 17, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Kristen B Long, Regina M Young, Alina C Boesteanu, Megan M Davis, J Joseph Melenhorst, Simon F Lacey, David A DeGaramo, Bruce L Levine, Joseph A Fraietta
Chimeric antigen receptor (CAR)-engineered T cells represent a breakthrough in personalized medicine. In this strategy, a patient's own T lymphocytes are genetically reprogrammed to encode a synthetic receptor that binds a tumor antigen, allowing T cells to recognize and kill antigen-expressing cancer cells. As a result of complete and durable responses in individuals who are refractory to standard of care therapy, CAR T cells directed against the CD19 protein have been granted United States Food and Drug Administration (FDA) approval as a therapy for treatment of pediatric and young adult acute lymphoblastic leukemia and diffuse large B cell lymphoma...
2018: Frontiers in Immunology
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
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
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
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
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