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Lymphoma & leukemia

Gunilla Enblad, Hannah Karlsson, Gustav Gammelgard, Jessica Wenthe, Tanja Lovgren, Rose-Marie Amini, Kristina I Wikstrom, Magnus Essand, Barbara Savoldo, Helene Hallbook, Martin Höglund, Gianpietro Dotti, Malcolm K Brenner, Hans Hagberg, Angelica Loskog
PURPOSE: CAR T cell therapy has been effective for patients with CD19+ B cell malignancies. Most studies have investigated second generation CARs with either CD28 or 4-1BB co-stimulatory domains in the CAR receptor. Here we describe the first clinical phase I/IIa trial using third generation CAR T cells targeting CD19 to evaluate safety and efficacy. EXPERIMENTAL DESIGN: Fifteen patients with B cell lymphoma or leukemia were treated with CAR T cells. The lymphoma patients received chemotherapy during CAR manufacture and eleven of fifteen were given low dose cyclophosphamide and fludarabine conditioning prior to CAR infusion...
August 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Khemayanto Hidayat, Hui-Juan Li, Bi-Min Shi
The associations between anthropometric factors and non-Hodgkin's lymphoma (NHL) risk remain inconclusive. A meta-analysis was performed to clarify these associations. PubMed and Web of Science were searched for relevant prospective observational studies. A random-effects model was used to generate the summary relative risks (RRs) with 95% confidence intervals (CIs). A total of 22 prospective cohort studies, with over 20,000 NHL cases, were included in the present meta-analysis. The summary RRs of NHL risk were 1...
September 2018: Critical Reviews in Oncology/hematology
P Puerta-Alcalde, Cardozo C, M Suárez-Lledó, O Rodríguez-Núñez, L Morata, C Fehér, F Marco, A Del Río, J A Martínez, J Mensa, M Rovira, J Esteve, A Soriano, C Garcia-Vidal
OBJECTIVES: We aimed to describe the current time to positivity (TTP) of blood cultures in onco-hematological patients with febrile neutropenia. We assessed the probability of having multidrug-resistant gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen...
August 7, 2018: Clinical Microbiology and Infection
T N Gibson, S Beeput, J Gaspard, C George, D Gibson, N Jackson, V Leandre-Broome, N Palmer-Mitchell, C Alexis, J Bird-Compton, C Bodkyn, R Boyle, S McLean-Salmon, M Reece-Mills, C Sin Quee-Brown, U Allen, S Weitzman, V Blanchette, S Gupta
BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. RESULTS: A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5...
August 9, 2018: Pediatric Blood & Cancer
Susan O'Brien, Manish Patel, Brad S Kahl, Steven M Horwitz, Francine M Foss, Pierluigi Porcu, Jeffrey Jones, Jan Burger, Nitin Jain, Kerstin Allen, Kerrie Faia, Mark Douglas, Howard M Stern, Jennifer Sweeney, Patrick Kelly, Virginia Kelly, Ian Flinn
Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment-naïve (TN) CLL. Per protocol, TN patients were at least 65 years old or had a del(17p)/TP53 mutation. Duvelisib was administered twice daily (BID) in 28-day cycles at doses of 8-75 mg in RR patients (n=55) and 25 mg in TN patients (n=18...
August 10, 2018: American Journal of Hematology
Moussab Damlaj, Riad El Fakih, Shahrukh K Hashmi
Recent advancements in cancer care, coupled with early detection and an aging population have resulted in significant growth of cancer survivors. Long term follow up of such survivors is essential given the heightened risk for development of late effects such as secondary neoplasms, cardiovascular disease or psychosocial dysfunction among others. As more patients with hematologic malignancies are cured or managed over protracted periods of time, awareness of such issues is paramount for the practicing clinicians for optimal patient management...
July 25, 2018: Blood Reviews
Preetha D Kamath, Jennifer L Abrahams, Jeong Hee Cho-Vega
Human T-cell lymphotropic virus-1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATLL), an aggressive malignancy of CD4+ T-lymphocytes. This virus is endemic to the Caribbean, Japan, and regions of South America and Africa.[1] In Miami/ South Florida, whose population is enriched with immigrants from HTLV-1 endemic areas, we have identified multiple cases of ATLL. [2] This article is protected by copyright. All rights reserved.
August 9, 2018: Journal of Cutaneous Pathology
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion...
July 2018: Journal of Cytology
Noriaki Kawano, Shuro Yoshida, Sayaka Kawano, Takuro Kuriyama, Yoshihiro Tahara, Atsushi Toyofuku, Tatsuya Manabe, Atsushi Doi, Soushi Terasaka, Kiyoshi Yamashita, Yuji Ueda, Hidenobu Ochiai, Kousuke Marutsuka, Yoshihisa Yamano, Kazuya Shimoda, Ikuo Kikuchi
Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1-associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear.We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016...
August 8, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
Irene Scarfò, Maria Ormhøj, Matthew J Frigault, Ana P Castano, Selena Lorrey, Amanda A Bouffard, Alexandria van Scoyk, Scott J Rodig, Alexandra J Shay, Jon C Aster, Frederic I Preffer, David M Weinstock, Marcela V Maus
Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment for patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets. Here, we report on the design and optimization of a novel CAR directed to the surface antigen CD37, which is expressed in B-cell non-Hodgkin Lymphomas, in chronic lymphocytic leukemia (CLL) and in some cases of cutaneous and peripheral T-cell lymphomas (CTCL and PTCL, respectively)...
August 8, 2018: Blood
Lisett Contreras, Ruben I Calderon, Armando Varela-Ramirez, Hong-Yu Zhang, Yuan Quan, Umashankar Das, Jonathan R Dimmock, Rachid Skouta, Renato J Aguilera
PURPOSE: Previously, compounds containing a piperidone structure have been shown to be highly cytotoxic to cancer cells. Recently, we found that the piperidone compound P2 exhibits a potent anti-neoplastic activity against human breast cancer-derived cells. Here, we aimed to evaluate two piperidone compounds, P1 and P2, for their potential anti-neoplastic activity against human leukemia/lymphoma-derived cells. METHODS: Cytotoxicity and apoptosis induction were evaluated using MTS, annexin V-FITC/PI and mitochondrial membrane potential polychromatic assays to confirm the mode of action of the piperidone compounds...
August 7, 2018: Cellular Oncology (Dordrecht)
Cristiane J Gomes-Lima, Yuri E Nikiforov, Wen Lee, Kenneth D Burman
Struma ovarii is a rare ovarian teratoma predominantly composed of thyroid tissue. The simultaneous presence of thyroid carcinoma in the struma ovarii and the thyroid gland is extremely rare. It remains unclear if these carcinomas represent independent primary tumors and whether the molecular mechanisms of the tumors developing in the thyroid and ovarian tissues are similar. We present the case of a patient with two independent papillary thyroid carcinomas (PTCs) in struma ovarii and the thyroid gland that are driven by different RAS mutations...
August 1, 2018: Journal of the Endocrine Society
Makoto Yamagishi, Dai Fujikawa, Toshiki Watanabe, Kaoru Uchimaru
Human T-cell leukemia virus type 1 (HTLV-1), the first reported human oncogenic retrovirus, is the etiologic agent of highly aggressive, currently incurable diseases such as adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 proteins, including Tax and HBZ, have been shown to have critical roles in HTLV-1 pathogenicity, yet the underlying mechanisms of HTLV-1-driven leukemogenesis are unclear. The frequent disruption of genetic and epigenetic gene regulation in various types of malignancy, including ATL, is evident...
2018: Frontiers in Microbiology
Mette Dahl, Iben Daugaard, Maria Schertz Andersen, Thomas Birkballe Hansen, Kirsten Grønbæk, Jørgen Kjems, Lasse Sommer Kristensen
Circular RNAs (circRNAs) are covalently closed endogenous molecules with tissue- and disease-specific expression patterns, which have potential as diagnostic and prognostic biomarkers in cancer. The molecules are formed by a backsplicing event linking the 3'-end of an exon to the 5'-end of the same or an upstream exon, and they exert diverse regulatory functions important in carcinogenesis. The landscape of circRNA expression has not been characterized in B-cell malignancies, and current methods for circRNA quantification have several limitations that prevent development of clinically applicable assays...
August 7, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kieu-Suong Le, Patricia Amé-Thomas, Karin Tarte, Françoise Gondois-Rey, Samuel Granjeaud, Florence Orlanducci, Etienne D Foucher, Florence Broussais, Reda Bouabdallah, Thierry Fest, Dominique Leroux, Sapna Yadavilli, Patrick A Mayes, Luc Xerri, Daniel Olive
A better characterization of T-cell subsets in the microenvironment of classical Hodgkin lymphoma (cHL) would help to develop immunotherapies. Using multicolor flow cytometry, we identified in 6 of 43 cHL tissue samples a previously unrecognized subset of CD8 T cells coexpressing CXCR5 and inducible T-cell costimulator (ICOS) molecules (CD8CXCR5+ICOS+ ). These cells shared phenotypic features with follicular helper T (TFH ) cells including low CCR7 expression together with high expression of B-cell lymphoma-6, programmed cell death 1, B and T lymphocyte attenuator, CD200, and OX40...
August 14, 2018: Blood Advances
Sofia Garces, Joseph D Khoury, Rashmi Kanagal-Shamanna, Alireza Salem, Sa A Wang, Chi Young Ok, Shimin Hu, Keyur P Patel, Mark J Routbort, Rajyalakshmi Luthra, Guilin Tang, Ellen J Schlette, Carlos E Bueso-Ramos, L Jeffrey Medeiros, Sanam Loghavi
The presence of expanded proliferation centers (PCs) in lymph nodes involved by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been associated with adverse clinical outcomes, but the frequency and significance of PCs in bone marrow (BM) remains unclear. The study group included 36 patients with BM involvement by CLL in which PCs were present. We compared this group with 110 randomly selected BM samples involved by CLL without morphologically discernable PCs. Patients with PCs in BM were younger (median age, 53years [range,18-71] versus 58years [range, 31-82]; P=...
August 4, 2018: Human Pathology
Hidemitsu Kurosawa, Akihiko Tanizawa, Hideki Muramatsu, Chikako Tono, Akihiro Watanabe, Haruko Shima, Masaki Ito, Yuki Yuza, Kazuko Hamamoto, Noriko Hotta, Masahiko Okada, Akiko Moriya Saito, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Keizo Horibe, Eiichi Ishii, Hiroyuki Shimada
BACKGROUND: The details of the sequential use of imatinib for first-line treatment followed by second-generation tyrosine kinase inhibitors (2G-TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G-TKIs following imatinib in pediatric chronic phase (CP)-CML. PROCEDURES: The Japanese Pediatric Leukemia/Lymphoma Study Group conducted a retrospective study of patients with newly diagnosed CML from 1996 to 2011...
August 7, 2018: Pediatric Blood & Cancer
O Olagoke, D Miller, F Hemmatzadeh, T Stephenson, J Fabijan, P Hutt, S Finch, N Speight, P Timms
Koala retrovirus (KoRV) infects the majority of Australia's koalas ( Phascolarctos cinereus ) and has been linked to several life-threatening diseases such as lymphoma and leukemia, as well as Chlamydia and thus poses a threat to the continued survival of this species. While quarantine and antiretroviral drug treatment are possible control measures, they are impractical, leaving vaccination as the only realistic option. In this study, we examined the effect of a recombinant envelope protein-based anti-KoRV vaccine in two groups of South Australian koalas: KoRV infected or KoRV free...
2018: NPJ Vaccines
Gaurav Narula, Maya Prasad, Shalini Jatia, Papagudi G Subramanian, Nikhil Patkar, Prashant Tembhare, Dhanlaxmi Shetty, Nehal Khanna, Siddharth Laskar, Tanuja Shet, Sridhar Epari, Seema Kembhavi, Sneha Shah, Sajid Qureshi, Sumeet Gujral, Shripad D Banavali
INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited...
October 2017: Indian Journal of Cancer
Tomohiro Kozako, Paolo Mellini, Takeo Ohsugi, Akiyoshi Aikawa, Yu-Ichiro Uchida, Shin-Ichiro Honda, Takayoshi Suzuki
BACKGROUND: Sirtuin 2 (SIRT2) is a member of the sirtuin family, nicotinamide adenine dinucleotide+ -dependent deacylases, which participates in modulation of cell cycle control, neurodegeneration, and tumorigenesis. SIRT2 expression increases in acute myeloid leukemia blasts. Downregulation of SIRT2 using siRNA causes apoptosis of HeLa cells. Therefore, selective inhibitors of SIRT2 are candidate therapeutic agents for cancer. Adult T-cell leukemia/lymphoma (ATL) is a T-cell malignancy that has a poor prognosis and develops after long-term infection with human T-cell leukemia virus (HTLV)-1...
August 6, 2018: BMC Cancer
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