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Chronic GVHD

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https://www.readbyqxmd.com/read/29353109/shortened-duration-tacrolimus-after-nonmyeloablative-hla-haploidentical-bmt
#1
Yvette L Kasamon, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Heather J Symons, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, Robert A Brodsky, William H Matsui, Ivan Borrello, Satish Shanbhag, Kenneth R Cooke, Richard F Ambinder, Leo Luznik, Javier Bolaños-Meade, Richard J Jones
With posttransplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative HLA-haploidentical (NMA haplo) and HLA-matched blood or marrow transplantation (BMT) have comparable outcomes. Early discontinuation of immunosuppression may reduce relapse, as well as improve immune reconstitution, but may increase GVHD. We conducted a prospective trial of NMA haplo BMT for patients with hematologic malignancies (median age, 61), evaluating the safety of early discontinuation of tacrolimus...
January 15, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29344728/-cutaneous-graft-versus-host-disease
#2
REVIEW
A Cho, U Just, R Knobler
BACKGROUND: Graft-versus-host disease (GvHD) is a complex multiorgan disease, which can occur as a complication following allogeneic stem cell transplantation. Involvement of the skin represents the most common appearance of GvHD. The role of the dermatologist is critical for diagnosis and initiation of treatment. OBJECTIVES: The aim of this article is to provide a comprehensive review of the cutaneous types of GvHD and to present the most recent data on diverse therapy options for its acute and chronic form allowing the clinician to establish a definite diagnosis and to initiate proper therapy...
January 17, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29335633/long-term-survival-among-patients-who-are-disease-free-at-1-year-post-allogeneic-hematopoietic-cell-transplantation-a-single-center-analysis-of-389-consecutive-patients
#3
Melhem M Solh, Asad Bashey, Scott R Solomon, Lawrence E Morris, Xu Zhang, Stacey Brown, H Kent Holland
Allogeneic hematopoietic cell transplantation (HCT) is associated with significant morbidity and mortality especially in the first year after HCT. In this study, we examine the long-term outcomes of patients who survived at least one year post HCT without evidence of relapse. We analyzed the records for 389 consecutive patients receiving an allogeneic transplant from 2005 to 2016 from a MRD, MUD, or haploidentical donor, who were alive and disease free at one year post-transplant. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29335631/impact-of-hla-allele-mismatch-at-hla-a-b-c-drb1-and-dqb1-on-outcomes-in-haploidentical-stem-cell-transplantation
#4
Ming-Rui Huo, Xu-Ying Pei, Dan Li, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
The impact of human leukocyte antigen (HLA) allele mismatch on transplant outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been established. We retrospectively studied 595 patients with hematologic malignancy who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B, -C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was analyzed. Greater number of HLA allele disparity does not appear worsen outcome. As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet engraftment (HR 0...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29334367/unmanipulated-haploidentical-transplantation-conditioning-with-busulfan-cyclophosphamide-and-anti-thymoglobulin-for-adult-severe-aplastic-anaemia
#5
L-P Xu, Z-L Xu, F-R Wang, X-D Mo, T-T Han, W Han, Y-H Chen, Y-Y Zhang, J-Z Wang, Y Wang, C-H Yan, Y-Q Sun, F-F Tang, X-H Zhang, X-J Huang
We conducted a retrospective analysis to evaluate outcomes of haploidentical transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults received haploidentical transplantation between May 2011 and December 2016. Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti-thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and peripheral blood transplantation. The patients' median age was 25 years. Forty-nine patients survived for more than 28 days and all achieved donor myeloid engraftment...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330405/better-outcome-with-haploidentical-over-hla-matched-related-donors-in-patients-with-hodgkin-s-lymphoma-undergoing-allogeneic-haematopoietic-cell-transplantation-a-study-by-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy
#6
Jordan Gauthier, Xavier Poiré, Anne-Claire Gac, Mathieu Leclerc, Thierry Guillaume, Yves Chalandon, Stéphanie Nguyen, Edouard Forcade, Caroline Régny, Jacques-Olivier Bay, Ali Bazarbachi, Pierre-Simon Rohrlich, Anne Huynh, Jonathan Farhi, Tony Marchand, Jean-Valère Malfuson, Sylvain Pilorge, Hélène Labussière-Wallet, Cécile Renard, Luc-Matthieu Fornecker, Marie Detrait, Rémy Duléry, Jérémy Delage, Anne-Lise Ménard, Amandine Charbonnier, Brigitte Nelken, Charlotte Jubert, Felipe Suarez, Régis Peffault de la Tour, Yves Beguin, Hélène Schoemans, Didier Blaise, Ibrahim Yakoub-Agha
The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between January 2011 and January 2016...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330391/impact-of-antithymocyte-globulin-doses-in-reduced-intensity-conditioning-before-allogeneic-transplantation-from-matched-sibling-donor-for-patients-with-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-european-group-of-bone-marrow-transplantation
#7
Raynier Devillier, Myriam Labopin, Patrice Chevallier, Marie-Pierre Ledoux, Gérard Socié, Anne Huynh, Jean-Henri Bourhis, Jean-Yves Cahn, Gabrielle Roth-Guepin, Ghulam Mufti, Déborah Desmier, Mauricette Michallet, Nathalie Fegueux, Fabio Ciceri, Fréderic Baron, Didier Blaise, Arnon Nagler, Mohamad Mohty
Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD) prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However, its use is still controversial in matched sibling donor (MSD) Allo-HSCT, notably after reduced intensity conditioning (RIC). ATG dose may influence the outcome, explaining in part the discordant conclusions in MSD Allo-HSCT. We, therefore, analyzed the impact of ATG doses in patients with acute myeloid leukemia in first complete remission undergoing RIC Allo-HSCT from a MSD...
January 12, 2018: Bone Marrow Transplantation
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
#8
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/29325829/allogeneic-stem-cell-transplantation-for-advanced-myelodysplastic-syndrome-comparison-of-outcomes-between-cd34-selected-or-unmodified-hematopoietic-stem-cells-transplants
#9
Roni Tamari, Betul Oran, Patrick Hilden, Molly Maloy, Piyanuch Kongtim, Esperanza B Papadopoulos, Gabriela Rondon, Ann A Jakubowski, Borje S Andersson, Sean M Devlin, Sairah Ahmed, Uday R Popat, Doris Ponce, Julianne Chen, Craig Sauter, James W Young, Marcos de Lima, Miguel-Angel Perales, Richard J O'Reilly, Sergio A Giralt, Richard E Champlin, Hugo Castro-Malaspina
PURPOSE: To compare transplant outcomes in patients with advanced myelodysplastic syndrome (MDS) after CD34+ selected or unmodified allografts. PATIENTS AND METHODS: This analysis included initially 181 patients; 60 underwent CD34+ selected transplant and 121 had an unmodified transplant. Due to significant differences in disease characteristics, the analysis was limited to patients who had <10% blasts prior to transplant (N=145). Two groups were defined: (1) low risk: good and intermediate risk cytogenetics (CD34+, N=39; unmodified, N=46), and (2) high risk: poor and very poor risk cytogenetic (CD34+, N=19; unmodified, N=41)...
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
#10
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
#11
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/29305194/cd34-selection-vs-reduced-intensity-conditioning-and-unmodified-graft-for-allogeneic-hematopoietic-cell-transplantation-in-patients-with-aml-and-mds-50-years
#12
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/29296875/vaccination-with-autologous-myeloblasts-admixed-with-gm-k562-cells-in-patients-with-advanced-mds-or-aml-after-allogeneic-hsct
#13
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/29296864/immune-tolerance-induction-by-nonmyeloablative-haploidentical-hsct-combining-t-cell-depletion-and-posttransplant-cyclophosphamide
#14
Franco Aversa, Esther Bachar-Lustig, Noga Or-Geva, Lucia Prezioso, Sabrina Bonomini, Ilenia Manfra, Alessandro Monti, Chiara Schifano, Yael Zlotnikov-Klionsky, Massimo F Martelli, Gabriella Sammarelli, Maria Sassi, Maurizio Soli, Silvia Giuliodori, Magda Benecchi, Nicola Giuliani, Frank Lohr, Silvia Pratissoli, Yair Reisner
The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296834/haploidentical-transplant-in-patients-with-myelodysplastic-syndrome
#15
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
#16
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
#17
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
#18
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/29296707/cyclophosphamide-improves-engraftment-in-patients-with-scd-and-severe-organ-damage-who-undergo-haploidentical-pbsct
#19
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
#20
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
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