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Graft-versus-host disease

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https://www.readbyqxmd.com/read/29159318/young-donor-white-blood-cell-immunotherapy-induces-extensive-tumor-necrosis-in-advanced-stage-solid-tumors
#1
Dipnarine Maharaj, Pedro G Vianna, Wendy Ward, Anthony J Messina, Trevor Rayborn, Jacqueline V Gouvea, Richard D Hammer, Zheng Cui
Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68-91% granulocytes) collected by leukapheresis from young, healthy donors (age 18-35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone...
October 2017: Heliyon
https://www.readbyqxmd.com/read/29156642/is-the-benefit-risk-ratio-for-patients-with-transfusion-dependent-thalassemia-treated-by-unrelated-cord-blood-transplantation-favorable
#2
REVIEW
Tang-Her Jaing
Transfusion-dependent thalassemia (TDT) is an inherited disorder characterized by absent or defective production of α- or β-hemoglobin chains. If untreated, the disease invariably culminates in death in early infancy due to cardiac failure or overwhelming infection. Although there is clear evidence of good health-related quality of life and return to normal life style, the choice to undergo hematopoietic stem cell transplantation (HSCT) remains a challenge because of the potential risk of transplant-related mortality (TRM) in TDT...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156204/autologous-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-an-obsolete-or-resurfacing-concept
#3
REVIEW
Hillard M Lazarus, Najla El Jurdi
Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapies such as hematopoietic cell transplantation (HCT), an increasingly utilized modality...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155367/predicted-indirectly-recognizable-hla-epitopes-are-not-associated-with-clinical-outcomes-after-haploidentical-hematopoietic-stem-cell-transplantation
#4
Ming-Rui Huo, Dan Li, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
Haploidentical stem cell transplantation (haplo-SCT) provides an alternative method to cure patients with malignant and nonmalignant hematologic diseases who lack a human leukocyte antigen (HLA) matched related or unrelated donor. HLA disparity between donor and patient was the main reason causing lots of clinical immune response. The aim of this study was to investigate whether indirect recognition of mismatched HLA could predict the clinical outcomes in haplo-SCT. The probability of indirect recognition was predicted by the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model...
November 16, 2017: Human Immunology
https://www.readbyqxmd.com/read/29155316/influence-of-age-on-acute-and-chronic-gvhd-in-children-receiving-hla-identical-sibling-bmt-for-acute-leukemia-implications-for-prophylaxis
#5
Muna Qayed, Tao Wang, Michael T Hemmer, Stephen Spellman, Mukta Arora, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Mahmoud Aljuf, Mouhab Ayas, Menachem Bitan, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, David Delgado, Robert Peter Gale, Gregory Hale, Haydar Frangoul, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Leslie Lehman, John Levine, Margaret MacMillan, David I Marks, Taiga Nishihori, Richard F Olsson, Peiman Hematti, Olov Ringden, Ayman Saad, Prakash Satwani, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Shalini Shenoy, Edmund K Waller, Lolie Yu, Mary M Horowitz, John Horan
Relapse remains the major cause of mortality post hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research suggests that reducing the intensity of calcineurin inhibitor based graft versus host disease (GVHD) prophylaxis may be an effective strategy in abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29155271/t-cell-replete-haploidentical-transplantation-in-acute-myeloid-leukemia
#6
Luca Castagna, Raynier Devillier, Norbert Vey, Didier Blaise
In the last decade, the number of haploidentical transplantation is enhanced and this because of the widespread use of T cell replete platforms, developed worldwide. Acute myeloid leukemia is the main indication to perform an allogeneic stem cell transplantation. In this paper, we reviewed the clinical results obtained using T cell replete platforms in different clinical situations such as first or further complete remission, refractory disease, and elderly population. Overall, the toxic profile of T cell replete haploidentical transplantation is similar to transplantation from other donors, with some positive aspects such as a reduced incidence of chronic graft versus host disease...
November 16, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29151581/human-pbmc-transferred-murine-mhc-class-i-ii-deficient-nog-mice-enable-long-term-evaluation-of-human-immune-responses
#7
Tomonori Yaguchi, Asuka Kobayashi, Takashi Inozume, Kenji Morii, Haruna Nagumo, Hiroshi Nishio, Takashi Iwata, Yuyo Ka, Ikumi Katano, Ryoji Ito, Mamoru Ito, Yutaka Kawakami
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg(null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29151133/treatment-of-relapsed-aml-and-mds-after-allogeneic-stem-cell-transplantation-with-decitabine-and-dli-a-retrospective-multicenter-analysis-on-behalf-of-the-german-cooperative-transplant-study-group
#8
Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11)...
November 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29150107/pre-sarcopenia-and-bone-mineral-density-in-adults-submitted-to-hematopoietic-stem-cell-transplantation
#9
Cristiane Pavan Pereira, Denise Johnsson Campos Amaral, Vaneuza Araujo Moreira Funke, Victória Zeghbi Cochenski Borba
BACKGROUND: The aim of this study was to evaluate the prevalence of pre-sarcopenia and bone mineral density after hematopoietic stem cell transplantation. METHODS: The study group consisted of over 18-year-old patients who had been submitted to allogeneic transplantation at least one year previously. Patients and healthy controls were matched by sex, ethnic background, age, and body mass index. Body composition and bone mineral density were measured by dual-energy X-ray absorptiometry...
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#10
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29147612/low-dose-post-transplant-cyclophosphamide-can-mitigate-gvhd-and-enhance-the-g-csf-atg-induced-gvhd-protective-activity-and-improve-haploidentical-transplant-outcomes
#11
Yu Wang, Ying-Jun Chang, Lu Chen, Lan-Ping Xu, Zhi-Lei Bian, Xiao-Hui Zhang, Chen-Hua Yan, Kai-Yan Liu, Xiao-Jun Huang
Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145997/correlation-of-graft-immune-composition-with-outcomes-after-allogeneic-stem-cell-transplantation-moving-towards-a-perfect-transplant
#12
REVIEW
Guang Gu, Jian-Zhu Yang, Li-Xia Sun
Allogeneic stem cell transplantation (allo-SCT) offers an important curative therapy for hematological malignancies and other diseases. A number of studies have demonstrated the association of immune compositions in allografts with outcomes after allo-SCT, which promote graft engineering to improve transplant prognosis. This review summarizes the advances in investigating the correlation of the graft immune compositions with transplant outcomes in different transplant modalities, focusing on the immune subsets likely to have the greatest impact on clinical outcomes...
November 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29143281/long-term-outcome-in-patients-treated-at-home-during-the-pancytopenic-phase-after-allogeneic-haematopoietic-stem-cell-transplantation
#13
Olle Ringdén, Behnam Sadeghi, Gianluca Moretti, Sigrun Finnbogadottir, Brita Eriksson, Jonas Mattsson, Britt-Marie Svahn, Mats Remberger
Patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) were given the option to be treated at home during the pancytopenic phase. Daily visits by a nurse and phone calls from a physician from the unit were part of the protocol. During almost two decades, 252 patients with haematological malignancies and non-malignant disorders were included. Median age was 47 (range 0-72) years. Myeloablative conditioning was given to 102 patients and reduced intensity to 150. Donors were matched unrelated (n = 160), HLA-identical siblings (n = 71), or HLA-mismatched (n = 21)...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29143249/next-generation-chimeric-antigen-receptor-t-cell-therapy-going-off-the-shelf
#14
Marco Ruella, Saad S Kenderian
Autologous, patient-specific chimeric antigen receptor T-cell (CART) therapy has emerged as a powerful and potentially curative therapy for cancer, especially for CD19-positive hematological malignancies. Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy approved by the Food and Drug Administration (FDA) for acute lymphoblastic leukemia. However, the development of CART technology and its wider application is partly limited by the patient-specific nature of such a platform and by the time required for manufacturing...
November 16, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29142307/genetic-polymorphism-related-to-monocyte-macrophage-function-is-associated-with-graft-versus-host-disease
#15
Kati Hyvärinen, Jarmo Ritari, Satu Koskela, Riitta Niittyvuopio, Anne Nihtinen, Liisa Volin, David Gallardo, Jukka Partanen
Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141887/apoptosis-in-mesenchymal-stromal-cells-induces-in-vivo-recipient-mediated-immunomodulation
#16
Antonio Galleu, Yanira Riffo-Vasquez, Cristina Trento, Cara Lomas, Luigi Dolcetti, Tik Shing Cheung, Malte von Bonin, Laura Barbieri, Krishma Halai, Sophie Ward, Ling Weng, Ronjon Chakraverty, Giovanna Lombardi, Fiona M Watt, Kim Orchard, David I Marks, Jane Apperley, Martin Bornhauser, Henning Walczak, Clare Bennett, Francesco Dazzi
The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141183/functional-outcomes-of-acute-inpatient-rehabilitation-in-patients-with-chronic-graft-versus-host-disease
#17
Jason Leung, Sean Smith, Claire Kalpakjian
BACKGROUND: Growing numbers of allogeneic stem cell transplants (HSCT) and improved post-transplant care have led to an increase of individuals with chronic graft versus host disease (cGVHD). Although cGVHD leads to functional impairment for many, there is limited literature regarding the benefits of acute inpatient rehabilitation for cGVHD patients. OBJECTIVE: To assess Functional Independence Measure (FIM) outcomes of cGVHD patients during acute inpatient rehabilitation, and to compare inpatient rehabilitation outcomes to burn patients, a rehabilitation patient population with similar co-morbidities...
November 12, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/29140823/single-center-retrospective-study-on-meibomian-gland-loss-in-patients-with-ocular-chronic-graft-versus-host-disease
#18
Lijuan Que, Xiaofeng Zhang, Mengmeng Li
OBJECTIVES: This study aimed to analyze the influencing factors of meibomian gland loss in patients with ocular chronic graft-versus-host disease (GVHD) and its correlation with other clinical ocular surface assessment indexes. METHODS: The clinical data of patients with ocular chronic GVHD from the ocular surface and corneal outpatient clinic of the First Affiliated Hospital of Soochow University were reviewed from June 2012 to June 2016. The relationship between the percentage of meibomian gland acinar area and the influencing factors, such as patient's sex, age, transplantation method, human leukocyte antigen (HLA) matching, the time when eye discomfort appeared after transplantation (month), and the severity of ocular chronic GVHD, was investigated...
November 14, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/29140544/a-cryptosporidium-infection-in-a-patient-with-relapsed-t-lymphoblastic-lymphoma-undergoing-allogeneic-stem-cell-transplantation
#19
Joanna Schiller, Sebastian Klein, Marianne Engels, Reinhard Büttner, Jan Rybniker, Gerd Fätkenheuer, Christof Scheid, Christian Wybranski, Alexander Quaas, Hans Christian Reinhardt, Ruth Waßermann
Cryptosporidium infection is a rare cause of enterocolitis. In immunocompromised patients, cryptosporidiosis may lead to debilitating and life-threatening diarrhea and malabsorption, occasionally with multi organ involvement. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) requires long-term immunosuppressive therapy, while cellular immunity is usually compromised due to intensive conditioning chemotherapy. Diarrhea in patients who underwent allo-HSCT may be a sign of an infection, but can also be the result of intestinal graft-versus-host disease (GvHD)...
November 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29139480/position-paper-the-potential-role-of-optical-biopsy-in-the-study-and-diagnosis-of-environmental-enteric-dysfunction
#20
REVIEW
Alex J Thompson, Michael Hughes, Salzitsa Anastasova, Laurie S Conklin, Tudor Thomas, Cadman Leggett, William A Faubion, Thomas J Miller, Peter Delaney, François Lacombe, Sacha Loiseau, Alexander Meining, Rebecca Richards-Kortum, Guillermo J Tearney, Paul Kelly, Guang-Zhong Yang
Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology...
November 15, 2017: Nature Reviews. Gastroenterology & Hepatology
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