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Raimon Duran-Struuck, Abraham J Matar, Rebecca L Crepeau, Alexander G S Teague, Benjamin M Horner, Vimukthi Pathiraja, Thomas R Spitzer, Jay A Fishman, Roderick T Bronson, David H Sachs, Christene A Huang
We previously described successful hematopoietic stem cell engraftment across MHC barriers in miniature swine without graft-versus-host disease (GVHD) using novel reduced-intensity conditioning regimens consisting of partial transient recipient T cell-depletion, thymic or low-dose total body irradiation, and a short course of cyclosporine A. Here we report that stable chimeric animals generated with these protocols are strongly resistant to donor leukocyte infusion (DLI)-mediated GVH effects. Of 33 total DLIs in tolerant chimeras at clinical doses, 21 failed to induce conversion to full donor hematopoietic chimerism or cause GVHD...
November 2016: Biology of Blood and Marrow Transplantation
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FOXP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
July 28, 2016: Oncotarget
Jessica Heinrichs, Jun Li, Hung Nguyen, Yongxia Wu, David Bastian, Anusara Daethanasanmak, M-Hanief Sofi, Steven Schutt, Chen Liu, Junfei Jin, Brian Betts, Claudio Anasetti, Xue-Zhong Yu
Adoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (Allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemia (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4(+) or CD8(+) T cells and tested their ability to suppress GVH and maintain GVL responses...
June 2016: Oncoimmunology
Marsela Qesari, Anne Richter, Justyna Ogonek, Eva Mischak-Weissinger, Xiao-Nong Wang, Anne M Dickinson
BACKGROUND: Graft-versus-host (GvH) disease (GvHD) remains a serious concern for patients undergoing antiviral cellular therapy. Despite the major improvements in cellular immunotherapy, the immunogenicity of virus-specific T cells has not yet been fully defined. This present study aims to examine how cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) respond to allogeneic antigen stimulation and whether they give rise to GvHD target tissue damage. METHODS: Cytomegalovirus-specific CTLs were isolated by the IFN-γ secretion assay (gamma-catch) from healthy seropositive volunteers and expanded in vitro...
May 5, 2016: Transplantation
Petya Apostolova, Robert Zeiser
Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative treatment approach for many patients with benign or malignant diseases of the hematopoietic system. However, post-transplant morbidity and mortality are significantly increased by the development of acute graft-versus-host disease (GvHD). While alloreactive T cells act as the main cellular mediator of the GvH reaction, recent evidence suggests a critical role of the innate immune system in the early stages of GvHD initiation...
February 19, 2016: Human Immunology
Badr Al-Bawardy, Emmanuel C Gorospe, Atif Saleem, Navtej S Buttar, Louis M Wong Kee Song
BACKGROUND AND AIM: Endoscopic injection of 2-octyl cyanoacrylate (2-OCA) is used on an off-label basis for gastric variceal hemorrhage (GVH) in the United States. We assessed the efficacy, safety, and predictors of rebleeding after gastric variceal obturation (GVO) with 2-OCA in patients with acute GVH. MATERIALS AND METHODS: A retrospective analysis was performed of patients with GVH who underwent 2-OCA injection for GVO over a 15-year period. Rates of acute hemostasis, predictors of rebleeding, and cyanoacrylate-related adverse events were assessed...
July 2016: Journal of Clinical Gastroenterology
P Rossi, A Delcampe, J Gueudry, A Duncombe, E Gabison, S Doan, M Muraine
INTRODUCTION: Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation. Severe keratoconjunctivitis sicca is common in patients with chronic GVH disease. The goal of this study was to evaluate the safety and efficacy of a gas-permeable scleral lens in the management of severe dry eye disease associated with chronic GVH. PATIENTS AND METHODS: This is a retrospective study from June 2009 to November 2013. Patients fitted with scleral lenses for severe keratoconjunctivitis sicca associated with chronic GVH were included...
November 2015: Journal Français D'ophtalmologie
Seung-Ah Yahng, Young-Woo Jeon, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Hee-Je Kim
This study explored the influence of mismatched inhibitory killer cell immunoglobulin-like receptor (KIR) ligands on the outcome of haploidentical transplantation using T cell-replete, granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in adult patients with acute myeloid leukemia (AML). Three groups were examined: unidirectional graft-versus-host KIR ligand mismatched (GVH-KIR-MM; n = 33), bidirectional KIR ligand matched (KIR-M; n = 41), and unidirectional host-versus-graft KIR ligand mismatched (HVG-KIR-MM; n = 26)...
February 2016: Biology of Blood and Marrow Transplantation
Ahmet Soysal
Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug...
2015: Infection and Drug Resistance
U L Dzhulakian, B V Biderman, E G Gemdzhian, A B Sudarikov, V G Savchenko
AIM: To determine the immunoglobulin variable heavy chain (gVH) genes and their somatic mutations and to compare these data with the clinical and laboratory parameters of patients and the outcomes of the disease. SUBJECTS AND METHODS: The investigation enrolled 24 patients (9 men and 15 women whose age was 32 to 77 years (median age, 60 years) with splenic marginal zone B-cell lymphoma (SMZBCL). The latter was diagnosed on the basis of histological and immunohistochemical examinations of a bone marrow trephine biopsy specimen, immunophenotyping of peripheral lymphoid cells or bone marrow aspirates...
2015: Terapevticheskiĭ Arkhiv
Yinmeng Yang, Elad Jacoby, Terry J Fry
PURPOSE OF REVIEW: As T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product. RECENT FINDINGS: The majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR...
November 2015: Current Opinion in Hematology
Chiara Francesca Magnani, Andrea Biondi, Ettore Biagi
PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (HSCT) is still partially ineffective in curing high-risk hematological malignancies, with estimates of relapse rates ranging from 40 to 50%. The purpose of this review is to discuss the emerging therapeutic options for patients with relapsed disease following HSCT based on adoptive immunotherapy using donor-derived T cells genetically engineered to express CD19-specific chimeric antigen receptors (CARs). RECENT FINDINGS: Adoptive cell therapy (ACT) with CAR-modified T cells represents an attractive therapeutic option for further enhancing the graft-versus-leukemia effect...
November 2015: Current Opinion in Hematology
Kelly N Ma, Aristomenis Thanos, James Chodosh, Ankoor S Shah, Iason S Mantagos
Cryopreserved amniotic membrane (AM) transplantation is an emerging technique that is becoming the gold standard for the management of acute Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN). We describe a novel surgical technique utilizing a single, large sheet of AM (5 x 10 cm) and a custom-made forniceal ring, which facilitates AM placement. Our technique is easy to use and minimizes suturing and manipulation of ocular tissues, resulting in decreased operative time...
January 2016: Ocular Surface
Lenneke F J van Groningen, Aleida M Liefferink, Anton F J de Haan, Nicolaas P M Schaap, J Peter Donnelly, Nicole M A Blijlevens, Walter J F M van der Velden
Steroid-refractory acute graft-versus-host disease (aGVHD) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). A protocol on the management of aGVHD was introduced in our center that incorporated a prospective study on combination therapy with inolimomab (anti-IL-2Rα) and etanercept (anti-tumor necrosis factor-α) for steroid-refractory aGVHD. We evaluated the efficacy and safety in 21 consecutively treated patients. The patients had developed refractory aGVHD after SCT (n = 16) or donor lymphocyte infusion (n = 5), and aGVHD was classified as severe in all patients, mostly due to gastrointestinal involvement stages 2 to 4...
January 2016: Biology of Blood and Marrow Transplantation
Andrew C Harris, Rachel Young, Steven Devine, William J Hogan, Francis Ayuk, Udomsak Bunworasate, Chantiya Chanswangphuwana, Yvonne A Efebera, Ernst Holler, Mark Litzow, Rainer Ordemann, Muna Qayed, Anne S Renteria, Ran Reshef, Matthias Wölfl, Yi-Bin Chen, Steven Goldstein, Madan Jagasia, Franco Locatelli, Stephan Mielke, David Porter, Tal Schechter, Zhanna Shekhovtsova, James L M Ferrara, John E Levine
Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials...
January 2016: Biology of Blood and Marrow Transplantation
C G Valentini, E R Nuzzolo, N Orlando, E Metafuni, M Bianchi, P Chiusolo, G Zini, L Teofili
Ocular chronic GVHD is efficaciously treated with autologous platelet-derived eye drops. We investigated the cytokine content of eye drops produced using a non-gelified lysate obtained from autologous platelet-rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma...
February 2016: Vox Sanguinis
Yongjun Jo, Jihyang Lim, Yonggoo Kim, Kyungja Han, Woo-Sung Min, Eun-Jee Oh
We analyzed CD4 T-lymphocytes ATP levels along with lymphocyte subsets in 160 samples from 111 post-allogeneic hematopoietic stem cell transplantation (alloHSCT) patients. In patients with stable status, ImmuKnow levels changed over time and the 6-month post-alloHSCT levels were significantly higher than those tested within 6 months post-alloHSCT (P < 0.001). Although, ImmuKnow levels for acute graft-versus-host disease (GVHD) or infection episodes were not significantly different compared to those for stable alloHSCT, the levels were correlated with specific lymphocyte subpopulations at different times; the results within 6 months post-alloHSCT showed low positive correlation with natural killer cell count (r = 0...
October 2015: Transplant Immunology
Heidi Hausmann, Vijaya R Bhatt, Ji Yuan, Lori J Maness, Apar K Ganti
Atypical chronic myeloid leukemia is a rare entity that presents diagnostic and therapeutic challenges. Traditionally utilized therapeutic agents such as hydroxyurea or interferon result in a median survival of approximately two years, thus warranting identification of better options. We report a 49-year-old Caucasian female, who presented with extreme leukocytosis (white blood cells of 148,300/µL) with left shift, severe anemia, and thrombocytopenia. Following a diagnosis of atypical chronic myeloid leukemia, she was started on intravenous decitabine...
September 15, 2015: Journal of Oncology Pharmacy Practice
Sally Arai, Joseph Pidala, Iskra Pusic, Xiaoyu Chai, Samantha Jaglowski, Nandita Khera, Jeanne Palmer, George L Chen, Madan H Jagasia, Sebastian A Mayer, William A Wood, Michael Green, Teresa S Hyun, Yoshihiro Inamoto, Barry E Storer, David B Miklos, Howard M Shulman, Paul J Martin, Stefanie Sarantopoulos, Stephanie J Lee, Mary E D Flowers
PURPOSE: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion...
January 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hisashi Yamamoto, Naoyuki Uchida, Yumiko Uchida, Aya Nishida, Hikari Ota, Kosei Kageyama, Izumi Nasu, Sachie Wada, Daisuke Kaji, Kazuya Ishiwata, Shinsuke Takagi, Masanori Tsuji, Yuki Asano-Mori, Naofumi Matsuno, Go Yamamoto, Kazuhiro Masuoka, Koji Izutsu, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Tadaaki Ito, Masahiro Hayashi, Shuichi Taniguchi
No abstract text is available yet for this article.
December 2015: Annals of Hematology
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