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Frederic Baron, Myriam Labopin, Annalisa Ruggeri, Jan J Cornelissen, Ellen Meijer, Henrik Sengeloev, Dietger Niederwieser, Marco R de Groot, Harry C Schouten, Noel-Jean Milpied, Didier Blaise, Bipin Savani, Eliane Gluckman, Mohamad Mohty, Arnon Nagler
PURPOSE: We assessed the impact of donor type in acute myeloid leukemia (AML) patients transplanted with 2 Gy total body irradiation (TBI)-based nonmyeloablative conditioning regimen. Experimental Design: Data from 1715 adult patients, with AML in CR1 or CR2 were included in this retrospective survey. RESULTS: Donors consisted either of HLA-matched sibling donors (MSD, n=701), 10/10 HLA-matched unrelated donors (MUD, n=611), HLA-haplo-identical donors (haplo, n=112) or single or double umbilical cord bloods (CBT, n=291)...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xia Zhou, Dayong Ding, Tingting You, Xun Zhang, Keiji Takabe, Feng Xu
As the main hemicellulose of poplar, the interaction of xylan with lignin was expected to have profound effect on biomass recalcitrance. In this paper, the dynamic changes of xylan and lignin in poplar cell wall during a mild pretreatment using γ-valerolactone (GVL) was investigated using chemical and microscopic techniques. Synergetic dissolution of branched xylan and lignin from the secondary wall of fibre cell was found to play a major role in openning the cell wall structure for enzymatic attack. In the case of the removal of xylan and lignin reaching a certain level, β-O-4' cleavage of lignin which destroyed its interaction with hydrophobic cellulose face was found to make great contribution to the enhanced enzymatic hydrolysis...
March 19, 2018: Journal of Agricultural and Food Chemistry
Ugur Sahin, Klara Dalva, Funda Gungor, Celalettin Ustun, Meral Beksac
Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene matching on transplant outcomes is still inconclusive. Recent data suggest that killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK cell) activity may contribute to graft versus leukemia (GvL) effects and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case-control study aims to evaluate the effects of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell replete HLA-identical sibling allo-HSCTs in a homogenous young patient population with myeloid leukemias...
March 16, 2018: Annals of Hematology
Changwei Hu, Hui Zhang, Xudong Liu, Jianmei Li, Zhicheng Jiang
In present work, the performances of solvents, including γ-butyrolactone (GBL), γ-valerolactone (GVL), tetrahydrofuran (THF), ethyl acetate (EAC), 2-methyl tetrahydrofuran (2-MeTHF), and the corresponding mixture with H2O, on the cleavage of inter- and intra-molecular linkages of lignin in corncob residue were investigated. At 200 oC miscible co-solvents (H2O-GBL, H2O-GVL and H2O-THF) exhibited much better efficiency for lignin dissolution than both immiscible co-solvents (H2O-EAC and H2O-2-MeTHF) and pure solvents...
March 15, 2018: ChemSusChem
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
Steven D Schutt, Yongxia Wu, Chih-Hang Anthony Tang, David Bastian, Hung Nguyen, M Hanief Sofi, MengMeng Zhang, Chen Liu, Kris Helke, Carole Wilson, Lynn M Schnapp, Juan R Del Valle, Chih-Chi Andrew Hu, Xue-Zhong Yu
Hematopoietic stem cell transplantation (HCT) is a curative procedure for hematological malignancies, but chronic graft-versus-host disease (cGVHD) remains a major complication after allogeneic HCT. Because donor B cells are essential for cGVHD development and B cells are sensitive to endoplasmic reticulum (ER) stress, we hypothesized that the IRE-1α/XBP-1 pathway is required for B-cell activation and function and for the development of cGVHD. To test this hypothesis, we used conditional knock-out mice deficient of XBP-1 specifically in B cells...
February 27, 2018: Blood Advances
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT...
February 22, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Laura Cudillo, Raffaella Cerretti, Alessandra Picardi, Benedetta Mariotti, Gottardo De Angelis, Maria Cantonetti, Massimiliano Postorino, Eleonora Ceresoli, Giovanna De Santis, Daniela Nasso, Francesco Pisani, Enrico Scala, Fabio Di Piazza, Alessandro Lanti
In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10...
February 13, 2018: Annals of Hematology
Akiyoshi Takami
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields a high rate of curability for acute myeloid leukemia (AML), it is also associated with transplant-related morbidity and mortality (TRM). The risk and severity of TRM increase with the use of an alternative donor graft in the absence of an HLA-matched sibling donor (MSD). With the declining birthrate and aging of the population, the numbers of patients with an MSD are decreasing, and alternative donor transplants, including the post-transplant cyclophosphamide method using haplo-identical donors, are increasing...
January 27, 2018: International Journal of Hematology
Ali Hussain Motagamwala, Wangyun Won, Canan Sener, David Martin Alonso, Christos T Maravelias, James A Dumesic
We report a process for converting fructose, at a high concentration (15 weight %), to 2,5-furandicarboxylic acid (FDCA), a monomer used in the production of polyethylene furanoate, a renewable plastic. In our process, fructose is dehydrated to hydroxymethylfurfural (HMF) at high yields (70%) using a γ-valerolactone (GVL)/H2O solvent system. HMF is subsequently oxidized to FDCA over a Pt/C catalyst with 93% yield. The advantage of our system is the higher solubility of FDCA in GVL/H2O, which allows oxidation at high concentrations using a heterogeneous catalyst that eliminates the need for a homogeneous base...
January 2018: Science Advances
Marcel van den Brink, Markus Uhrberg, Lorenz Jahn, John F DiPersio, Michael A Pulsipher
The graft vs. leukemia (GvL) effect as a method of preventing relapse is well described after allogeneic hematopoietic cell transplantation (HCT), but the mechanisms to this effect and how tumor sometimes develops resistance to GvL are just beginning to be understood. This article reviews and expands upon data presented at the Third International Workshop on Biology, Prevention and Treatment of Relapse after Stem Cell Transplantation held in Hamburg, Germany, in November 2016. We first discuss in detail the role that T-cell impairment early after HCT plays in relapse by looking at data from T cell-depleted approaches as well as the clear role that early T-cell recovery has shown in improving outcomes...
January 24, 2018: Bone Marrow Transplantation
Kate Markey, Rachel D Kuns, Daniel J Browne, Kate H Gartlan, Renee J Robb, J Paulo Martins, Andrea S Henden, Simone A Minnie, Melody Cheong, Motoko Koyama, Mark J Smyth, Raymond J Steptoe, Gabrielle Belz, Thomas Brocker, Mariapia A Degli-Esposti, Steven W Lane, Geoffrey R Hill
PURPOSE: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunological graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD. EXPERIMENTAL DESIGN: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DC in controlling donor T cell mediated GVHD and GVL...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Stella Robert, Jörn C Albring, Karin Frebel, Corinna Opitz, Jennifer Urh, Claudia Wolf, Christine Heinrich, Wolfgang E Berdel, Matthias Stelljes
Durable remissions of hematological malignancies regularly observed following allogeneic hematopoietic stem cell transplantation (aHSCT) are due to the conditioning regimen, as well as an immunological phenomenon called graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. The development of GVL is closely linked to graft-versus-host disease (GVHD), the main side effect associated with aHSCT. Both, GVHD and GVL are mediated by donor T cells that are initially activated by antigen-presenting cells that present recipient-derived alloantigens in the context of either matched or mismatched MHC class I molecules...
January 23, 2018: Bone Marrow Transplantation
Robert Zeiser
No abstract text is available yet for this article.
January 22, 2018: Blood
Rupert Handgretinger, Karin Schilbach
Allogeneic hematopoetic stem cell transplantation (HCT) offers an option for patients with hematologic malignancies, in whom conventional standard therapies failed or are not effective enough to cure the disease. Successful HCT is able to restore functional hematopoiesis and immune function and the new donor-derived immune system can exert a graft-versus-leukemia (GvL) effect. However, allogenic HCT can also be associated with serious risks for transplantation-related morbidities or mortalities like graft versus host disease (GvHD) or life-threatening infectious complications...
January 22, 2018: Blood
Scott Bottoms, Quinn Dickinson, Mick McGee, Li Hinchman, Alan Higbee, Alex Hebert, Jose Serate, Dan Xie, Yaoping Zhang, Joshua J Coon, Chad L Myers, Robert Landick, Jeff S Piotrowski
BACKGROUND: Gamma valerolactone (GVL) treatment of lignocellulosic bomass is a promising technology for degradation of biomass for biofuel production; however, GVL is toxic to fermentative microbes. Using a combination of chemical genomics with the yeast (Saccharomyces cerevisiae) deletion collection to identify sensitive and resistant mutants, and chemical proteomics to monitor protein abundance in the presence of GVL, we sought to understand the mechanism toxicity and resistance to GVL with the goal of engineering a GVL-tolerant, xylose-fermenting yeast...
January 12, 2018: Microbial Cell Factories
LaQuisa Hill, Amin Alousi, Partow Kebriaei, Rohtesh Mehta, Katayoun Rezvani, Elizabeth Shpall
Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality...
January 2018: Therapeutic Advances in Hematology
Luke Maggs, Francesca Kinsella, Y L Tracey Chan, Suzy Eldershaw, Duncan Murray, Jane Nunnick, Joanne Bird, Charles Craddock, Jianmin Zuo, Ram Malladi, Paul Moss
The graft-versus-leukemia (GVL) effect of allogeneic hemopoietic stem cell transplantation (allo-HSCT) is mediated by the donor immune system and acts to decrease the rate of disease relapse. Although studies of posttransplant immune reconstitution have identified correlates of clinical outcome, the number and profile of mature immune cells infused with the stem cell graft is also likely to be an important determinant and has been relatively poorly studied. We characterized immune cells within the stem cell graft of 107 patients who underwent T-cell-depleted allo-HSCT and related this to clinical outcome...
August 22, 2017: Blood Advances
Mark A Schroeder, Jaebok Choi, Karl Staser, John F DiPersio
For patients with hematologic malignancies, allogeneic hematopoietic cell transplantation (alloHCT) offers a potential curative treatment option, primarily due to an allogeneic immune response against recipient tumor cells (ie, graft-versus-leukemia [GVL] activity). However, many recipients of alloHCT develop graft-versus-host disease (GVHD), in which allogeneic immune responses lead to the damage of healthy tissue. GVHD is a leading cause of nonrelapse mortality and a key contributor to morbidity among patients undergoing alloHCT...
December 28, 2017: Biology of Blood and Marrow Transplantation
Yuan Song, Bo Hu, Yonghao Liu, Ziqi Jin, Yinsheng Zhang, Dandan Lin, Ying Zhu, Lei Lei, Huanle Gong, Yu Mei, Huey Yee Teo, Depei Wu, Haiyan Liu
Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo...
December 27, 2017: European Journal of Immunology
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