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Lymphoblastic T cell lymphoma

Wei Zhang, Kimberly R Jordan, Brian Schulte, Enkhtsetseg Purev
Background: Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating acute lymphoblastic leukemia and non-Hodgkin's lymphoma with high rate complete responses. However, the broad clinical application of CAR T-cell therapy has been challenging, largely due to the lack of widespread ability to produce and high cost of CAR T-cell products using traditional methods of production. Automated cell processing in a closed system has emerged as a potential method to increase the feasibility of producing CAR T cells locally at academic centers due to its minimal reliance on experienced labor, thereby making the process less expensive and more consistent than traditional methods of production...
2018: Drug Design, Development and Therapy
J Rao, M Ruan, B H Yu, X Q Li, W T Yang, R H Shui
Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes...
October 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Ping Wang, Xian'gui Peng, Xiaojuan Deng, Li Gao, Xi Zhang, Yimei Feng
RATIONALE: The diagnosis of hematological malignancies depends on laboratory analysis and often requires multiple experimental methods to judge, otherwise misdiagnosis is apt to happen. Lymph node biopsy immunohistochemistry (IHC) for T-lymphoblastic lymphoma (T-LBL) requires the establishment of antibody set screening. For identifying T-LBL and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) by lymph node biopsy and IHC, WHO has not yet proposed a better IHC antibody combination...
October 2018: Medicine (Baltimore)
Zong Zhang, Wei Gui, Min Bai, Li Ma, Li-Ping Su, Tao Guan
OBJECTIVE: To investigate the diagnosis and treatment of patients with T-lymphoblastic lymphoma(T-LBL)combined with acute myeloid leukemia(AML). METHODS: The clinical features of 4 patients with T-LBL combined with AML were retrospectively analyzed, Among them the case 1 and 2 were synchronous occurrence,and case 3 and 4 were sequentially occurred. Especially for former 2 patients,the dliagnosis differentiated from the involved lymph node of AML is important...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jacob S Appelbaum, Filippo Milano
PURPOSE OF REVIEW: Cellular therapy using T cells modified to express chimeric antigen receptors (CAR-T cells) has had striking success in patients that have failed previous treatment for CD19+ B cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or acute lymphoblastic leukemia (ALL). Curative therapy for this group of diseases has previously been limited to allogeneic hematopoietic cell transplantation HCT (alloHCT). The recent results of CAR-T cell therapy raise the question of how best to integrate CAR-T cell therapy and alloHCT in the care of these patients...
October 2, 2018: Current Hematologic Malignancy Reports
Charlotte Graham, Agnieszka Jozwik, Andrea Pepper, Reuben Benjamin
Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). However, there are limitations, including inability to manufacture CAR-T cells from the patient's own T cells, disease progression and death prior to return of engineered cells. T cell dysfunction is known to occur in cancer patients, and several groups have recently described differences in CAR-T cells generated from chronic lymphocytic leukaemia (CLL) patients compared with those from a healthy donor...
October 1, 2018: Cells
Marinella N Ghezzo, Mónica T Fernandes, Ivette Pacheco-Leyva, Pedro M Rodrigues, Rui S Machado, Marta A S Araújo, Ravi K Kalathur, Matthias E Futschik, Nuno L Alves, Nuno R Dos Santos
T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphomas (T-LBL) are aggressive malignancies of thymocytes. The role of thymic microenvironmental cells and stromal factors in thymocyte malignant transformation and T-ALL development remains little explored. Here, using the TEL-JAK2 transgenic (TJ2-Tg) mouse model of T-ALL/LBL, which is driven by constitutive JAK/STAT signaling and characterized by the acquisition of Notch1 mutations, we sought to identify stromal cell alterations associated with thymic leukemogenesis...
September 26, 2018: Carcinogenesis
Wen Zheng, Yuhuan Gao, Xiaoyan Ke, Weijing Zhang, Liping Su, Hanyun Ren, Ningjing Lin, Yan Xie, Meifeng Tu, Weiping Liu, Lingyan Ping, Zhitao Ying, Chen Zhang, Lijuan Deng, Xiaopei Wang, Yuqin Song, Jun Zhu
BACKGROUND: The combination of chemotherapy and L-asparaginase (L-ASP) treatment significantly increased survival rate in an adult patient with extranodal natural killer (NK)/T-cell lymphoma (NKTCL). However, hypersensitivity reactions of L-ASP in some patients limited its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and longer circulating half-life than unconjugated L-ASP, and has been reported to be effective and well-tolerated in children with acute lymphoblastic leukemia...
September 21, 2018: BMC Cancer
Marie Émilie Dourthe, Karima Yakouben, Delphine Chaillou, Emmanuelle Lesprit, Jean-Hugues Dalle, André Baruchel
Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease...
September 17, 2018: Bulletin du Cancer
Leena T Rahmat, Anna Nguyen, Haifaa Abdulhaq, Sonam Prakash, Aaron C Logan, Gabriel N Mannis
Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine...
2018: Case Reports in Hematology
Matthew Walters, Mark R Pittelkow, Robert P Hasserjian, Nancy Lee Harris, William R Macon, Paul J Kurtin, Karen L G Rech
Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT...
September 15, 2018: American Journal of Surgical Pathology
Yanfen Liu, Xinfeng Chen, Dao Wang, Hong Li, Jianmin Huang, Zhen Zhang, Yingjin Qiao, Hongling Zhang, Ying Zeng, Chao Tang, Shuangning Yang, Xiaochun Wan, Youhai H Chen, Yi Zhang
Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3...
November 2018: Journal of Immunotherapy
Tatsuaki Watanabe, Hideo Shimomura, Tatsushi Mutoh, Ryoko Saito, Ryoi Goto, Takehiro Yamada, Hirotsugu Notsuda, Yasushi Matsuda, Masafumi Noda, Akira Sakurada, Yasuyuki Taki, Yoshinori Okada
PURPOSE: The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. METHODS: A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17-84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution...
September 10, 2018: Surgery Today
Aleksei Titov, Alexey Petukhov, Alena Staliarova, Dmitriy Motorin, Emil Bulatov, Oleg Shuvalov, Surinder M Soond, Mauro Piacentini, Gerry Melino, Andrey Zaritskey, Nickolai A Barlev
Currently, immunotherapy is attracting a lot of attention and may potentially become a leading approach in the treatment of cancer. One emerging therapeutic, the chimeric-antigen receptor T-cell adoptive immunotherapy (CAR-T) is showing remarkable efficacy in the treatment of several B-cell malignancies. The popularity of CAR-T has been founded on two CAR T-cell products recently approved by FDA (during 2017) in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia and B-cell lymphoma. However, their toxicities observed in clinical trials were extremely significant and in some cases even fatal with no approved algorithms for toxicity prediction being available to date...
September 4, 2018: Cell Death & Disease
Ndiya Ogba, Nicole M Arwood, Nancy L Bartlett, Mara Bloom, Patrick Brown, Christine Brown, Elizabeth Lihua Budde, Robert Carlson, Stephanie Farnia, Terry J Fry, Morgan Garber, Rebecca A Gardner, Lauren Gurschick, Patricia Kropf, Jeff J Reitan, Craig Sauter, Bijal Shah, Elizabeth J Shpall, Steven T Rosen
Patients with relapsed or refractory (R/R) cancers have a poor prognosis and limited treatment options. The recent approval of 2 chimeric antigen receptor (CAR) autologous T-cell products for R/R B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma treatment is setting the stage for what is possible in other diseases. However, there are important factors that must be considered, including patient selection, toxicity management, and costs associated with CAR T-cell therapy. To begin to address these issues, NCCN organized a task force consisting of a multidisciplinary panel of experts in oncology, cancer center administration, and health policy, which met for the first time in March 2018...
September 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Kentaro Ohki, Nobutaka Kiyokawa, Yuya Saito, Shinsuke Hirabayashi, Kazuhiko Nakabayashi, Hitoshi Ichikawa, Yukihide Momozawa, Kohji Okamura, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto, Motohiro Kato, Keitaro Fukushima, Daisuke Hasegawa, Hiroko Fukushima, Masako Imai, Ryosuke Kajiwara, Takashi Koike, Isao Komori, Atsushi Matsui, Makiko Mori, Koichi Moriwaki, Yasushi Noguchi, Myoung-Ja Park, Takahiro Ueda, Shohei Yamamoto, Koichi Matsuda, Teruhiko Yoshida, Kenji Matsumoto, Kenichiro Hata, Michiaki Kubo, Yoichi Matsubara, Hiroyuki Takahashi, Takashi Fukushima, Yasuhide Hayashi, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara
Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remains unknown. We identified 16 acute lymphoblastic leukemia cases and 1 lymphoma case harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6) and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial...
August 31, 2018: Haematologica
Jingshu Meng, Chan Chang, Huaxiong Pan, Fang Zhu, Yin Xiao, Tao Liu, Xiu Nie, Gang Wu, Liling Zhang
Distribution of different malignant lymphoma subtypes varies substantially in different geographic regions, even in different districts in China.In order to estimate the epidemiologic characteristics of malignant lymphoma in Hubei, China, we retrospectively analyzed a total number of 2027 newly diagnosed cases from April 2009 to April 2014 in a single institution according to the 2008 WHO classification.The median diagnosis age of all these lymphoma patients was 53 (1-99) years, and the median ages for non-(NHL) and Hodgkin lymphoma (HL) were 54 (1-99) years and 38 (5-84) years, respectively...
August 2018: Medicine (Baltimore)
Yang Jiang, Abhishek Maiti, Zeyad Kanaan
No abstract text is available yet for this article.
August 20, 2018: American Journal of Medicine
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
Zijun Zhao, Yu Chen, Ngiambudulu M Francisco, Yuanqing Zhang, Minhao Wu
Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma...
July 2018: Acta Pharmaceutica Sinica. B
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