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Don M. Benson

Filiz Yucebay, Christina Matthews, Marcin Puto, Junan Li, Basem William, Samantha M Jaglowski, Sam L Penza, Sumithira Vasu, Don M Benson, Leslie A Andritsos, Steven M Devine, Yvonne A Efebera, Julianna V F Roddy
Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria...
February 15, 2019: Leukemia & Lymphoma
Sara Singer, Nidhi Sharma, Robert Dean, Qiuhong Zhao, Donna Abounader, Patrick Elder, Craig C Hofmeister, Don M Benson, Ashley Rosko, Sam Penza, Leslie Andritsos, Sumithira Vasu, Samantha Jaglowski, Basem M William, Brian Bolwell, Brad Pohlman, Matt Kalaycio, Deepa Jagadeesh, Brian Hill, Ronald Sobecks, Steven M Devine, Navneet S Majhail, Yvonne A Efebera
High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We sought to compare the two regimens for patients with relapsed NHL undergoing AHCT...
February 4, 2019: Bone Marrow Transplantation
Sara Singer, Robert Dean, Qiuhong Zhao, Nidhi Sharma, Donna Abounader, Patrick Elder, Craig C Hofmeister, Don M Benson, Ashley Rosko, Sam Penza, Leslie Andritsos, Sumithira Vasu, Samantha Jaglowski, Basem M William, Brian Bolwell, Brad Pohlman, Matt Kalaycio, Deepa Jagadeesh, Brian Hill, Ronald Sobecks, Steven M Devine, Navneet S Majhail, Yvonne A Efebera
High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) is a standard of care for patients with relapsed Hodgkin's lymphoma (HL). Different conditioning regimen prior to AHSCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We retrospectively compared the outcomes of patients treated with BEAM (N=128) or BUCYVP16 (N=105) followed by AHSCT. After a median follow up of 4...
February 1, 2019: Biology of Blood and Marrow Transplantation
Yufeng Wang, Yibo Zhang, Ping Yi, Wenjuan Dong, Ansel P Nalin, Jianying Zhang, Zheng Zhu, Lichao Chen, Don M Benson, Bethany L Mundy-Bosse, Aharon G Freud, Michael A Caligiuri, Jianhua Yu
Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells1 . Here we identified a signaling pathway-involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes2,3 -that was activated in response to IL-15 in human NK cells. IL-15 induced the phosphorylation of AKT, which led to the deubiquitination, increased stability and nuclear accumulation of XBP1s protein. XBP1s bound to and recruited the transcription factor T-BET to the gene encoding granzyme B, leading to increased transcription...
January 2019: Nature Immunology
Sharla M Wells-Di Gregorio, Donald R Marks, Joseph DeCola, Juan Peng, Danielle Probst, Alexandra Zaleta, Don Benson, David E Cohn, Maryam Lustberg, William E Carson, Uly Magalang
OBJECTIVE: This study evaluated a three-session acceptance-based cognitive behavioral -acceptance and commitment therapy (CBT-ACT) intervention targeting a common symptom cluster in advanced cancer-worry-insomnia-depression-fatigue. METHODS: Twenty-eight patients with advanced cancer were randomly assigned to the CBT-ACT intervention or waitlist. At preintervention, participants completed a psychodiagnostic interview, standardized questionnaires, and a sleep diary...
October 18, 2018: Psycho-oncology
Sonya John, Nidhi Sharma, Douglas W Sborov, Nita Williams, Desirée Jones, Don M Benson, Yvonne A Efebera, Ashley E Rosko, Jennifer Vincent, Craig C Hofmeister
No abstract text is available yet for this article.
October 2, 2018: Leukemia & Lymphoma
Steven D Scoville, Ansel P Nalin, Luxi Chen, Li Chen, Michael H Zhang, Kathleen McConnell, Susana Beceiro Casas, Gabrielle Ernst, Abd Al-Rahman Traboulsi, Naima Hashi, Monica Williams, Xiaoli Zhang, Tiffany Hughes, Anjali Mishra, Don M Benson, Jennifer N Saultz, Jianhua Yu, Aharon G Freud, Michael A Caligiuri, Bethany L Mundy-Bosse
Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing natural killer (NK) cell development and NK cell function. This is driven in part by the overexpression of microRNA (miR)-29b in the NK cells of AML patients, but how this occurs is unknown. In the current study, we demonstrate that the transcription factor aryl hydrocarbon receptor (AHR) directly regulates miR-29b expression. We show that human AML blasts activate the AHR pathway and induce miR-29b expression in NK cells, thereby impairing NK cell maturation and NK cell function, which can be reversed by treating NK cells with an AHR antagonist...
October 25, 2018: Blood
Ashley E Rosko, Ying Huang, Don M Benson, Yvonne A Efebera, Craig Hofmeister, Samantha Jaglowski, Steven Devine, Geetika Bhatt, Tanya M Wildes, Alanna Dyko, Desirée Jones, Michelle J Naughton, John C Byrd, Christin E Burd
Multiple myeloma (MM) is a disease of aging adults and autologous stem cell transplant (ASCT) is considered the standard of care. As the population ages a growing number of older adults will undergo ASCT and an objective approach to estimate physiologic reserve and transplant morbidity risk is warranted. Here, we evaluate assess p16INK4a (p16), a molecular aging biomarker, along with geriatric metrics to determine risk of transplant toxicity. METHODS: We prospectively evaluated 100 MM patients for frailty before and after ASCT using a Geriatric Assessment (GA) and collected T-cells for analysis of p16 using a custom nanostring codeset...
July 5, 2018: Journal of Geriatric Oncology
Nathaniel J Buteyn, Kavin Fatehchand, Ramasamy Santhanam, Huiqing Fang, Gino M Dettorre, Shalini Gautam, Bonnie K Harrington, Sally E Henderson, Giovanna Merchand-Reyes, Xiaokui Mo, Don M Benson, William E Carson, Sumithira Vasu, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) remains a significant health problem, with poor outcomes despite chemotherapy and bone marrow transplants. Although one form of AML, acute promyelocytic leukemia (APL), is successfully treated with all-trans retinoic acid (ATRA), this drug is seemingly ineffective against all other forms of AML. Here, we show that ATRA up-regulates CD38 expression on AML blasts to sufficient levels that promote antibody-mediated fratricide following the addition of anti-CD38 daratumumab (DARA). The combination of ATRA plus DARA induced Fc-dependent conjugate formation and cytotoxicity among AML blasts in vitro...
July 24, 2018: International Immunology
Wing Keung Chan, Siwen Kang, Youssef Youssef, Erin N Glankler, Emma R Barrett, Alex M Carter, Elshafa H Ahmed, Aman Prasad, Luxi Chen, Jianying Zhang, Don M Benson, Michael A Caligiuri, Jianhua Yu
Multiple myeloma (MM) is an incurable hematologic malignancy of plasma cells, with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single-chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb). Although NKG2D is a potent activation receptor ubiquitously expressed on mostly cytolytic immune cells including NK cells, CD8+ T cells, γδ T cells, and NKT cells, the CS1 tumor-associated antigen on MM represents a promising target...
July 2018: Cancer Immunology Research
Hallie Barr, Jessica Dempsey, Allyson Waller, Ying Huang, Nita Williams, Nidhi Sharma, Don M Benson, Ashley E Rosko, Yvonne A Efebera, Craig C Hofmeister
No abstract text is available yet for this article.
November 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A Caligiuri, Don M Benson, Jianhua Yu
Purpose: Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer (NK) cells. Experimental Design: Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells...
August 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Thomas Martin, Rachid Baz, Don M Benson, Nikoletta Lendvai, Jeffrey Wolf, Pamela Munster, Alexander M Lesokhin, Claudine Wack, Eric Charpentier, Frank Campana, Ravi Vij
This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone...
June 22, 2017: Blood
Douglas W Sborov, Alessandro Canella, Erinn M Hade, Xiaokui Mo, Soun Khountham, Jiang Wang, Wenjun Ni, Ming Poi, Christopher Coss, Zhongfa Liu, Mitch A Phelps, Amir Mortazavi, Leslie Andritsos, Robert A Baiocchi, Beth A Christian, Don M Benson, Joseph Flynn, Pierluigi Porcu, John C Byrd, Flavia Pichiorri, Craig C Hofmeister
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively...
October 2017: Leukemia & Lymphoma
Don M Benson
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
Kavin Fatehchand, Elizabeth L McMichael, Brenda F Reader, Huiqing Fang, Ramasamy Santhanam, Shalini Gautam, Saranya Elavazhagan, Payal Mehta, Nathaniel J Buteyn, Giovanna Merchand-Reyes, Sumithira Vasu, Xiaokui Mo, Don M Benson, James S Blachly, William E Carson, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFNγ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFNγ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of FcγRI, which mediates effector responses to therapeutic antibodies...
December 2, 2016: Journal of Biological Chemistry
Flavia Pichiorri, Sung-Suk Suh, Alberto Rocci, Luciana De Luca, Cristian Taccioli, Ramasamy Santhanam, Wenchao Zhou, Don M Benson, Craig Hofmainster, Hansjuerg Alder, Michela Garofalo, Gianpiero Di Leva, Stefano Volinia, Huey-Jen Lin, Danilo Perrotti, Michael Kuehl, Rami I Aqeilan, Antonio Palumbo, Carlo M Croce
No abstract text is available yet for this article.
August 8, 2016: Cancer Cell
Sumithira Vasu, Susan Geyer, Anissa Bingman, Jeffery J Auletta, Samantha Jaglowski, Pat Elder, Lynn C O'Donnell, Hillary Bradbury, Rhonda Kitzler, Leslie Andritsos, William Blum, Rebecca Klisovic, Sam Penza, Yvonne Efebera, Craig Hofmeister, Don M Benson, Natarajan Muthusamy, Gerard Lozanski, Steven M Devine
No abstract text is available yet for this article.
July 2016: Biology of Blood and Marrow Transplantation
Andrew Stiff, Enrico Caserta, Douglas W Sborov, Gerard J Nuovo, Xiaokui Mo, Sarah Y Schlotter, Alessandro Canella, Emily Smith, Joseph Badway, Matthew Old, Alena Cristina Jaime-Ramirez, Pearlly Yan, Don M Benson, John C Byrd, Robert Baiocchi, Balveen Kaur, Craig C Hofmeister, Flavia Pichiorri
Multiple myeloma remains incurable and the majority of patients die within 5 years of diagnosis. Reolysin, the infusible form of human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis and a virus-mediated antitumor immune response. Results from our phase I clinical trial investigating single agent Reolysin in patients with relapsed multiple myeloma confirmed tolerability, but no objective responses were evident, likely because the virus selectively entered the multiple myeloma cells but did not actively replicate...
May 2016: Molecular Cancer Therapeutics
Sean W Harshman, Alessandro Canella, Paul D Ciarlariello, Kitty Agarwal, Owen E Branson, Alberto Rocci, Hector Cordero, Mitch A Phelps, Erinn M Hade, Jason A Dubovsky, Antonio Palumbo, Ashley Rosko, John C Byrd, Craig C Hofmeister, Don M Benson, Michael E Paulaitis, Michael A Freitas, Flavia Pichiorri
UNLABELLED: Multiple myeloma (MM) is a hematological malignancy of clonal plasma cells in the bone marrow (BM). The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of extracellular vesicles (EVs). The aim of this manuscript is to use proteomic profiling of EVs as a tool to identify circulating tumor associated markers in MM patients. First, we characterized the EV protein content obtained from different MM cell lines...
March 16, 2016: Journal of Proteomics
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