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Chronic graft versus host

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https://www.readbyqxmd.com/read/29344728/-cutaneous-graft-versus-host-disease
#1
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/29341972/ocular-surface-and-tear-film-characteristics-in-a-sclerodermatous-chronic-graft-versus-host-disease-mouse-model
#2
Jingliang He, Mio Yamane, Shinsuke Shibata, Masaki Fukui, Eisuke Shimizu, Tetsuya Yano, Shin Mukai, Yutaka Kawakami, Shaowei Li, Kazuo Tsubota, Yoko Ogawa
PURPOSE: To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model. METHODS: The ocular surface features and tear film parameters of the mouse model were assessed by histopathology, immunohistochemistry, electron microscopy, quantitative polymerase chain reaction, and flow cytometry. RESULTS: The mice exhibited loss of body weight and decreased tear secretion (P < 0...
January 16, 2018: Cornea
https://www.readbyqxmd.com/read/29330402/chronic-graft-versus-host-disease-features-in-double-unit-cord-blood-transplantation-according-to-national-institutes-of-health-2005-cgvhd-consensus-criteria
#3
Hiromi Hayashi, Annalisa Ruggeri, Fernanda Volt, Jan J Cornelissen, Gerard Socié, Henrik Sengeloev, Mauricette Michallet, Dimitrios Karakasis, Eefke Petersen, Jean Yves Cahn, Hendrik Veelken, Mélanie Mercier, Pierre-Simon Rohrlich, Hanadi Rafii, Chantal Kenzey, Erick Xavier, Rafael F Duarte, Grzegorz W Basak, Vanderson Rocha, Eliane Gluckman
No abstract text is available yet for this article.
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29326124/bortezomib-based-immunosuppression-after-reduced-intensity-conditioning-hematopoietic-stem-cell-transplantation-randomized-phase-ii-results
#4
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
#5
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
#6
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
#7
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
#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/29296872/chronic-disease-burden-and-frailty-in-survivors-of-childhood-hsct-a-report-from-the-st-jude-lifetime-cohort-study
#11
Hesham M Eissa, Lu Lu, Malek Baassiri, Nickhill Bhakta, Matthew J Ehrhardt, Brandon M Triplett, Daniel M Green, Daniel A Mulrooney, Leslie L Robison, Melissa M Hudson, Kirsten K Ness
Outcomes of hematopoietic stem cell transplantation (HSCT) have markedly improved over the past 2 decades, underscoring a need to better understand the long-term health effects of this intensive treatment modality. We describe the burden of chronic medical conditions and frail health among St. Jude Lifetime Cohort Study participants treated for childhood hematologic malignancies with HSCT (n = 112) or with conventional therapy (n = 1106). Chronic conditions and frail health were ascertained clinically and classified according to a modified version of the Common Terminology Criteria for Adverse Events (version 4...
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
#12
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/29296838/phase-1-study-of-the-hedgehog-pathway-inhibitor-sonidegib-for-steroid-refractory-chronic-graft-versus-host-disease
#13
Zachariah DeFilipp, Rosalynn M Nazarian, Areej El-Jawahri, Shuli Li, Jami Brown, Candice Del Rio, Melissa Smith, Betsy Valles, Karen K Ballen, Steven L McAfee, Jacalyn Rosenblatt, Joseph H Antin, Corey S Cutler, Yi-Bin Chen
Hedgehog signaling plays a key role in tissue fibrosis, the pathological hallmark of chronic graft-versus-host disease (cGVHD). We conducted a phase 1 trial of sonidegib, a selective antagonist of the hedgehog coreceptor Smoothened, for the treatment of steroid-refractory cGVHD. After a 3+3 study design, sonidegib was administered for up to 12 cycles of 28 days each, using 3 doses: 200 mg/day (dose level 1), 400 mg/day (dose level 2), and 600 mg/day (dose level 3). Seventeen patients were enrolled. The median number of cycles completed was 6 (range, 0-12)...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296834/haploidentical-transplant-in-patients-with-myelodysplastic-syndrome
#14
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
#15
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
#16
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
#17
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/29296723/atg-vs-thiotepa-with-busulfan-and-cyclophosphamide-in-matched-related-bone-marrow-transplantation-for-thalassemia
#18
Lawrence Faulkner, Cornelio Uderzo, Sadaf Khalid, Priya Marwah, Rajpreet Soni, Naila Yaqub, Samina Amanat, Itrat Fatima, Sarah Khan Gilani, Tatheer Zahra, Stalin Ramprakash, Lallindra Gooneratne, Ruwangi Dissanayake, Senani Williams, Wasantha Rathnayake, Reshma Srinivas, Amit Sedai, Ankita Kumari, Lailith Parmar, Rakesh Dhanya, Rajat Kumar Agarwal
Matched-related bone marrow transplantation (BMT) may cure >80% of low-risk children with severe thalassemia (ST). Very long-term follow-up studies have shown how the standard busulfan-cyclophosphamide (BuCy) regimen may be associated with normalization of health-related quality of life, no second malignancies in the absence of chronic graft-versus-host disease, and fertility preservation in many patients. However, because BuCy may be associated with high rejection rates, some centers incorporate thiotepa (Tt) in busulfan- or treosulfan-based regimens, a combination that may increase the risk of permanent infertility...
May 23, 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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