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Acute graft versus host disease

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https://www.readbyqxmd.com/read/29330757/-myelodysplastic-syndrome-acute-leukemia-and-stem-cell-transplantation
#1
REVIEW
M Schmalzing, M Aringer, M Bornhäuser, J Atta
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders. They are characterized by inefficient hematopoiesis leading to peripheral cytopenia of one or more lineages and a variable risk of transformation into acute myeloid leukemia. They may either arise de novo as well as following exposition to environmental toxins, previous radiotherapy or chemotherapy or in the context of autoinflammatory diseases and related therapy. Characteristic cytogenetic abnormalities, along with the numbers of hematopoietic lineages affected and bone marrow blasts, enable an assessment of the risk of leukemic transformation...
October 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29330269/central-nervous-system-graft-versus-host-disease-cns-gvhd-after-allogeneic-haematopoietic-stem-cell-transplantation
#2
Karolina Polchlopek Blasiak, Federico Simonetta, Maria-Isabel Vargas, Yves Chalandon
A 60-year-old man presented with impaired consciousness and psychomotor agitation after a second allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor for acute myeloid leukaemia. Clinical, biological and radiological evidence suggested a diagnosis of central nervous system graft-versus-host disease (CNS-GvHD). After intrathecal infusion of methylprednisolone, the clinical symptoms as well as the radiological abnormalities disappeared. The present report illustrates the difficulties in the diagnosis and the management of CNS-GvHD, a very rare and still challenging neurological complication that can occur after allogeneic HSCT...
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29326124/bortezomib-based-immunosuppression-after-reduced-intensity-conditioning-hematopoietic-stem-cell-transplantation-randomized-phase-ii-results
#3
John Koreth, Haesook T Kim, Paulina B Lange, Samuel J Poryanda, Carol G Reynolds, Sharmila Chamling Rai, Philippe Armand, Corey S Cutler, Vincent T Ho, Brett Glotzbecker, Rushdia Yusuf, Sarah Nikiforow, Yi-Bin Chen, Bimalangshu Dey, Malgorzata McMasters, Jerome Ritz, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Edwin P Alyea
A prior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after HLA-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft versus host disease incidence, with promising overall and progression-free survival. We performed an open-label 3-arm 1:1:1 phase II randomized-controlled-trial comparing grade II-IV acute graft versus host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B); and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic transplantation recipients lacking HLA-matched related donors...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29325830/blood-and-marrow-transplant-clinical-trials-network-report-on-development-of-novel-endpoints-and-selection-of-promising-approaches-for-graft-versus-host-disease-prevention-trials
#4
Marcelo C Pasquini, Brent Logan, Richard J Jones, Amin M Alousi, Frederick R Appelbaum, Javier Bolaños-Meade, Mary E D Flowers, Sergio Giralt, Mary M Horowitz, David Jacobsohn, John Koreth, John E Levine, Leo Luznik, Richard Maziarz, Adam Mendizabal, Steven Pavletic, Miguel-Angel Perales, David Porter, Ran Reshef, Daniel Weisdorf, Joseph H Antin
Graft versus host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here, we report a benchmark analysis to evaluate the performance of six GVHD prevention strategies tested at single institutions compared to a large multicenter outcomes database as a control. Each intervention was compared to the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS) and chronic GVHD, relapse-free survival (CRFS)...
January 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29317998/new-and-emerging-therapies-for-acute-and-chronic-graft-versus-host-disease
#5
REVIEW
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
https://www.readbyqxmd.com/read/29316837/ruxolitinib-for-the-treatment-of-patients-with-steroid-refractory-gvhd-an-introduction-to-the-reach-trials
#6
Madan Jagasia, Robert Zeiser, Michael Arbushites, Patricia Delaite, Brian Gadbaw, Nikolas von Bubnoff
For patients with hematologic malignancies and disorders, allogeneic hematopoietic stem cell transplantation offers a potentially curative treatment option. Many patients develop graft-versus-host disease (GVHD), a serious complication and leading cause of nonrelapse mortality. Corticosteroids are the standard first-line treatment for GVHD; however, patients often become steroid-refractory or remain corticosteroid-dependent. New second-line treatment options are needed to improve patient outcomes. Here we review the role of JAK1 and JAK2 in acute and chronic GVHD...
January 10, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29311761/plasma-vascular-non-inflammatory-molecule-3-is-associated-with-gastrointestinal-acute-graft-versus-host-disease-in-mice
#7
Na Wang, Xiaoyi Qin, Yigeng Cao, Bin Liang, Kang Yu, Haige Ye
Background: Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD. Methods: We used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29305194/cd34-selection-vs-reduced-intensity-conditioning-and-unmodified-graft-for-allogeneic-hematopoietic-cell-transplantation-in-patients-with-aml-and-mds-50-years
#8
Pere Barba, Rodrigo Martino, Qin Zhou, Christina Cho, Hugo Castro-Malaspina, Sean Devlin, Albert Esquirol, Sergio Giralt, Ann A Jakubowski, Dolores Caballero, Molly Maloy, Esperanza B Papadopoulos, José Luís Piñana, María Laura Fox, Francisco Márquez, David Valcárcel, Carlos Solano, Lucía López-Corral, Jorge Sierra, Miguel-Angel Perales
Reduced-intensity conditioning (RIC) and t-cell depletion (TCD) through CD34+ selection without the use of post-transplant immunosuppression are 2 strategies used to reduce non-relapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of both approaches (RIC and TCD), we evaluated the outcomes of AML and MDS patients > 50 years who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable between patients receiving TCD (n=204) and RIC (n=151) except for more unrelated donors (68% vs...
January 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29304116/the-sorafenib-anti-relapse-effect-after-allohsct-is-associated-with-heightened-alloreactivity-and-accumulation-of-cd8-pd-1-cd279-lymphocytes-in-marrow
#9
Andrzej Lange, Emilia Jaskula, Janusz Lange, Grzegorz Dworacki, Dorota Nowak, Aleksandra Simiczyjew, Monika Mordak-Domagala, Mariola Sedzimirska
We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia...
2018: PloS One
https://www.readbyqxmd.com/read/29296875/vaccination-with-autologous-myeloblasts-admixed-with-gm-k562-cells-in-patients-with-advanced-mds-or-aml-after-allogeneic-hsct
#10
Vincent T Ho, Haesook T Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C Souders, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Jerome Ritz, Glenn Dranoff, Robert J Soiffer
We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (∼day 100)...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296867/long-term-control-of-recurrent-or-refractory-viral-infections-after-allogeneic-hsct-with-third-party-virus-specific-t-cells
#11
Barbara Withers, Emily Blyth, Leighton E Clancy, Agnes Yong, Chris Fraser, Jane Burgess, Renee Simms, Rebecca Brown, David Kliman, Ming-Celine Dubosq, David Bishop, Gaurav Sutrave, Chun Kei Kris Ma, Peter J Shaw, Kenneth P Micklethwaite, David J Gottlieb
Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296834/haploidentical-transplant-in-patients-with-myelodysplastic-syndrome
#12
Marie Robin, Raphael Porcher, Fabio Ciceri, Maria Teresa van Lint, Stella Santarone, Gerhard Ehninger, Didier Blaise, Zafer Güllbas, Soledad Gonzáles Muñiz, Mauricette Michallet, Andrea Velardi, Linda Koster, Johan Maertens, Jorge Sierra, Dominik Selleslag, Aleksandar Radujkovic, José L Díez-Martin, Lothar Kanz, Concepcion Herrera Arroyo, Dietger Niederwieser, He Huang, Andrew McDonald, Theo de Witte, Yener Koc, Nicolaus Kröger
The only curative treatment in patients with intermediate or high-risk myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), which usually results in a long-term, disease-free survival rate of between 30% and 50%, depending on the disease risk and the type of donor. In patients without an HLA-matched sibling donor, a family haploidentical donor is an alternative option. The present study reports the European Group for Blood and Marrow Transplantation activity for haploidentical transplantation in MDS patients...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296777/hla-mismatched-unrelated-donor-transplantation-using-tli-atg-conditioning-has-a-low-risk-of-gvhd-and-potent-antitumor-activity
#13
Michael A Spinner, Marcelo Fernández-Viña, Lisa E Creary, Olivia Quinn, Linda Elder, Sally Arai, Laura J Johnston, Everett H Meyer, David B Miklos, Lori S Muffly, Robert S Negrin, Judith A Shizuru, Wen-Kai Weng, Ginna G Laport, Samuel Strober, Robert Lowsky, Andrew R Rezvani
Many patients lack a fully HLA-matched donor for hematopoietic cell transplantation (HCT), and HLA mismatch is typically associated with inferior outcomes. Total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is a nonmyeloablative conditioning regimen that is protective against graft-versus-host disease (GVHD), and we hypothesized that the protective effect would extend beyond HLA-matched donors. We report outcomes for all consecutively transplanted patients at Stanford University from December 2001 through May 2015 who received TLI-ATG conditioning and HCTs from 8 to 9 out of 10 HLA-mismatched unrelated donors (MMUDs, N = 72) compared with 10 out of 10 HLA-matched unrelated donors (MUDs, N = 193)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296761/alternative-donor-hematopoietic-stem-cell-transplantation-for-sickle-cell-disease
#14
Andrew L Gilman, Michael J Eckrich, Stacy Epstein, Carrie Barnhart, Mark Cannon, Tracy Fukes, Michelle Hyland, Krishna Shah, Darci Grochowski, Elizabeth Champion, Anastasia Ivanova
Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell-depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296747/single-umbilical-cord-blood-with-or-without-cd34-cells-from-a-third-party-donor-in-adults-with-leukemia
#15
Jaime Sanz, Mi Kwon, Guiomar Bautista, Miguel A Sanz, Pascual Balsalobre, José Luis Piñana, Carlos Solano, Rafael Duarte, Christelle Ferrá, Ignacio Lorenzo, Carmen Martín, Pere Barba, María Jesús Pascual, Rodrigo Martino, Jorge Gayoso, Ismael Buño, Carmen Regidor, Almudena de la Iglesia, Juan Montoro, José Luis Díez-Martín, Guillermo F Sanz, Rafael Cabrera
We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34+ cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Español de Trasplante Hematopoyético. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296709/the-impact-of-hla-matching-on-outcomes-of-unmanipulated-haploidentical-hsct-is-modulated-by-gvhd-prophylaxis
#16
Francesca Lorentino, Myriam Labopin, Katharina Fleischhauer, Fabio Ciceri, Carlheinz R Mueller, Annalisa Ruggeri, Avichai Shimoni, Martin Bornhäuser, Andrea Bacigalupo, Zafer Gülbas, Yener Koc, William Arcese, Benedetto Bruno, Johanna Tischer, Didier Blaise, Giuseppe Messina, Dietrich W Beelen, Arnon Nagler, Mohamad Mohty
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with unmanipulated grafts is increasingly adopted for high-risk acute leukemia, with acute graft-versus-host disease (aGVHD) prophylaxis based on antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCy) as main platforms. No consensus exists on selection criteria over several haploidentical donors. We evaluated the impact of donor-recipient antigenic and allelic HLA-A, -B, -C, and -DRB1 mismatches on mismatched haplotype on outcomes of 509 unmanipulated haplo-HSCTs performed for acute leukemia under a PTCy (N = 313) or ATG (N = 196) regimen...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296707/cyclophosphamide-improves-engraftment-in-patients-with-scd-and-severe-organ-damage-who-undergo-haploidentical-pbsct
#17
Courtney D Fitzhugh, Matthew M Hsieh, Tiffani Taylor, Wynona Coles, Katherine Roskom, Delon Wilson, Elizabeth Wright, Neal Jeffries, Christopher J Gamper, Jonathan Powell, Leo Luznik, John F Tisdale
Peripheral blood stem cell transplantation (PBSCT) offers a curative option for sickle cell disease (SCD). Although HLA-matched sibling transplantation is promising, the vast majority of patients lack such a donor. We sought to develop a novel nonmyeloablative HLA-haploidentical PBSCT approach that could safely be used for patients with severe organ damage. Based on findings in our preclinical model, we developed a phase 1/2 trial using alemtuzumab, 400 cGy total body irradiation, and escalating doses of posttransplant cyclophosphamide (PT-Cy): 0 mg/kg in cohort 1, 50 mg/kg in cohort 2, and 100 mg/kg in cohort 3...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289756/the-role-of-janus-kinase-signaling-in-graft-versus-host-disease-and-graft-versus-leukemia
#18
REVIEW
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
https://www.readbyqxmd.com/read/29288898/cxcr3-blockade-combined-with-cyclosporine-a-alleviates-acute-graft-versus-host-disease-by-inhibiting-alloreactive-donor-t-cell-responses-in-a-murine-model
#19
Shengchao Miao, Bo Tang, Huihui Liu, Zhenhua Wang, Yongjin Shi, Yujun Dong, Wei Liu, Chenchen Qin, Hanyun Ren
Chemotaxis of T cells to acute graft-versus-host disease (aGvHD) target tissues directed by chemokines and their receptors plays a key role in the pathogenesis of aGvHD. Blockade of lymphocyte migration by targeting chemokine receptors may be a viable strategy for the prevention and treatment of aGvHD, which is quite distinguishable from typical efforts to use immunosuppressive medications that have been associated with some side effects. CXCR3 and its ligands have been reported to be correlated with aGvHD pathogenesis...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29288821/reduced-intensity-allogeneic-transplant-for-acute-myeloid-leukemia-and-myelodysplastic-syndrome-using-combined-cd34-selected-haploidentical-graft-and-a-single-umbilical-cord-unit-compared-to-matched-unrelated-donor-stem-cells-in-older-adults
#20
Stephanie B Tsai, Joanna Rhodes, Hongtao Liu, Tsiporah Shore, Michael Bishop, Melissa M Cushing, Usama Gergis, Lucy Godley, Justin Kline, Richard A Larson, Sebastian Mayer, Olatoyosi Odenike, Wendy Stock, Amittha Wickrema, Koen van Besien, Andrew S Artz
Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor cells (MUD) or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced intensity conditioning (RIC) with fludarabine and melphalan and antibody-mediated T-cell depletion for AML (n=83) or high risk MDS (n=26) followed by either a MUD (n=68) or haplo/cord (n=41) graft...
December 27, 2017: Biology of Blood and Marrow Transplantation
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