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Adult large T cell Lymphoma

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
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 2 or more prior therapies. As the first CAR T-cell therapy available for adults in the United States (U.S.), 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 & METHODS: We developed a decision model to estimate life years (LYs), quality-adjusted life years (QALYs), and lifetime cost for adult patients with R/R LBCL treated with axi-cel versus salvage chemotherapy (R-DHAP)...
September 27, 2018: Journal of Medical Economics
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
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)
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
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
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
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
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
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
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)
Chethan K Belludi, Edward T Qian, James J Tolle, Ryan M Brown, Mary Ann Thompson, Ridas Juskevicius
Anaplastic large cell lymphoma (ALCL) is a lymphoma of T-cell origin, characterized by the presence of large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped nuclei (hallmark cells), as well as strong and uniform expression of cluster of differentiation (CD)30. Two distinct clinicopathologic categories of ALCL include primary cutaneous ALCL and systemic ALCL. Systemic ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive, ALK-negative, and breast implant-associated ALCL...
July 17, 2018: Laboratory Medicine
Dana Hoser, Christian Schön, Christoph Loddenkemper, Philipp Lohneis, Anja A Kühl, Thomas Sommermann, Thomas Blankenstein, Gerald Willimsky
To date, little is known about the interaction between (pre-)malignant B cells and T cells. We generated transgenic mice that allow B cell-specific induction of the oncogene SV40 large T-antigen (TAg) to analyze the role of oncogene-specific T cells during sporadic B-cell lymphoma development. Constitutive TAg expression in CD19-Cre × LoxP-Tag mice resulted in TAg-tolerant CD8+ T cells and development of B-cell lymphomas. In contrast, CD19-CreERT2 × LoxP-Tag mice retained TAg-competent CD8+ T cells at time of oncogene induction and TAg expression in few B cells of adult mice resulted in exceptionally rare lymphoma formation late in life...
August 30, 2018: Blood
Dai Chihara, Nathan H Fowler, Yasuhiro Oki, Michelle A Fanale, Loretta J Nastoupil, Jason R Westin, Luis E Fayad, Sattva S Neelapu, Chan Yoon Cheah
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal presentation of lymphoma; however, the data for outcomes of patients with subtypes other than diffuse large B-cell lymphoma (DLBCL) are limited. Therefore, we analyzed overall survival (OS) of adult patients diagnosed with PCNSL by histologic subtype between 1998 and 2014 using the Surveillance, Epidemiology and End Results. A total of 4375 patients were identified. The median age of the patients was 64 years (range: 18-96)...
June 22, 2018: Oncotarget
Cristiane R Ferreira, Shuchun Zhao, Malaya K Sahoo, Benjamin Pinsky, Jenna Weber, Luis A P C Lage, Juliana Pereira, Maria C N Zerbini, Yasodha Natkunam
Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining...
June 10, 2018: Human Pathology
Koichi Ohshima, Hiroaki Miyoshi, Kyohei Yamada
Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T cells and shows variable biological and clinical presentations. The survival rate of patients with AITL did not correlate with T-cell clonality, the presence of EBV-infected cells, EBV-DNA copy number, or IgH rearrangements. However, tumor-associated macrophage/M2 macrophages significantly correlated with worse overall survival (OS). Additionally, patients with composite lymphoma with diffuse large B cell lymphoma and AITL showed worse OS...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
P Sharma, G T King, S S Shinde, E Purev, A Jimeno
B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options...
March 2018: Drugs of Today
Marshall Williams, Maria Eugenia Ariza
The Epstein-Barr virus (EBV), which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2), which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function...
May 1, 2018: Cancers
Cyrus Askin, Ashley Burris, Clifton Layman, Brian Haney, Jordan Hall
Secondary hemophagocytic lymphohistiocytosis (HLH) in adults is a rare, often fatal syndrome characterized by widespread immune dysregulation. It is seen as a complication of infections, autoimmune diseases, and malignancies. Among the malignancy-related causes, aggressive T-cell or NK-cell neoplasms are most notable, while B-cell lymphomas are less commonly implicated. We present the case of a 32-year-old male transferred to our facility with concern for HLH. During the first week of his hospitalization, his diagnosis was confirmed and the patient demonstrated spontaneous improvement in his symptoms prompting us to delay therapy while searching for a primary cause...
2018: Case Reports in Oncological Medicine
Hideki Hasegawa, Kaori Sano, Akira Ainai, Tadaki Suzuki
Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by infection of human T-cell leukemia virus type I (HTLV-I). Although the pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy resistance of ATL leads the poor prognosis of this disease. In order to understand the pathogenesis and establish an animal model useful for therapy attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal promoter to restrict the Tax expression in T-cells...
May 2018: Advances in Biological Regulation
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