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Acute GVHD

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https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#1
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28527984/personalized-prognostic-risk-score-for-long-term-survival-for-children-with-acute-leukemia-after-allogeneic-transplant
#2
Menachem Bitan, Kwang Woo Ahn, Heather R Millard, Michael A Pulsipher, Hisham Abdel-Azim, Jeffery J Auletta, Valerie Brown, Ka Wah Chan, Miguel Angel Diaz, Andrew Dietz, Marta González Vincent, Gregory Guilcher, Gregory A Hale, Robert J Hayashi, Amy Keating, Parinda Mehta, Kasiani Myers, Kristin Page, Tim Prestidge, Nirali N Shah, Angela R Smith, Ann Woolfrey, Elizabeth Thiel, Stella M Davies, Mary Eapen
We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML; n=790) and acute lymphoblastic leukemia (ALL; n=1096), transplanted between 2000 and 2010, who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease- and transplantation characteristics and acute and chronic graft versus host disease (GVHD) were performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival...
May 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28527401/prognostic-factors-on-graft-versus-host-disease-free-and-relapse-free-survival-after-allogeneic-hematopoietic-stem-cell-transplantation-for-adults-with-acute-leukemia
#3
Jie Tan, Ya Wang, Si-Jian Yu, Yong-Yong Ma, Hu-Yi Lei, Qi-Fa Liu
The cure of acute leukemia by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is closely linked to major complications leading to adverse outcomes, including graft-versus-host disease (GVHD), disease relapse and death. This study retrospectively investigated a consecutive series of 312 adult patients with acute leukemia receiving allo-HSCT by using a novel concept of GVHD-free/relapse-free survival (GRFS), and further evaluated the impact of clinical factors on GRFS. Results indicated that the 1- and 2-year GRFS were 54...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28504665/upper-gi-gvhd-similar-outcomes-to-other-grade-ii-graft-versus-host-disease
#4
R S Mehta, Q Cao, S Holtan, M L MacMillan, D J Weisdorf
The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD) compared with other grade II aGVHD is not clearly defined. We compared the outcomes of patients with grade II aGVHD with or without biopsy-proven UGI involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall response (ORR) to steroids at day 28 differed among the three groups (76, 67 and 91%, respectively, P=0.01), but was only marginally different in direct comparison with those without or with UGI aGVHD (P=0...
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28499937/haploidentical-allogeneic-hematopoietic-cell-transplantation-for-multiple-myeloma-using-post-transplant-cyclophosphamide-gvhd-prophylaxis
#5
Luca Castagna, Alberto Mussetti, Raynier Devillier, Alida Dominietto, Magda Marcatti, Giuseppe Milone, Francesco Maura, Chiara de Philippis, Benedetto Bruno, Sabine Furst, Didier Blaise, Paolo Corradini, Vittorio Montefusco
Allogeneic Hematopoietic Cell Transplantation (allo-HCT) currently represents the only potentially curative therapy for patients affected by multiple myeloma (MM). Up to 30% of patients in western countries do not have a matched donor. Haploidentical HCT (haplo-HCT) may be an option, but currently, there is are available data regarding this treatment. We analyzed survival outcomes of 30 heavily pretreated MM patients who received haplo-HCT with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host-disease (GVHD) prophylaxis...
May 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28499936/ucbt-without-antithymocyte-globulin-results-in-similar-survival-but-better-quality-of-life-compared-with-upbsct-for-the-treatment-of-acute-leukemia-a-retrospective-study-in-china
#6
J Tong, L Xuan, Y L Sun, D P Huang, H L Liu, C C Zheng, X Y Zhu, B L Tang, K D Song, X H Zhang, L Zhang, W Yao, D J Lin, Q F Liu, Z M Sun
While previous studies have demonstrated improved outcomes in umbilical cord blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the conditioning regimen, this approach has not been comparatively studied in unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the risks and benefits between UCBT without ATG and UPBSCT in patients with acute leukemia (AL). This was a multicenter retrospective study of 79 patients who underwent UCBT (myeloablative conditioning without ATG) and 96 patients who underwent UPBSCT (myeloablative conditioning with ATG)...
May 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28498033/development-and-characterization-of-novel-monoclonal-antibodies-against-human-dnam-1
#7
Genki Okumura, Fumie Abe, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human...
May 12, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28495642/feasibility-of-lenalidomide-therapy-for-persistent-chronic-lymphocytic-leukemia-after-allogeneic-transplantation
#8
Maria R Khouri, Elias J Jabbour, Alison M Gulbis, Francesco Turturro, Celina Ledesma, Martin Korbling, Barry I Samuels, Sairah Ahmed, Amin M Alousi, Stefan O Ciurea, David Marin, Krina K Patel, Uday R Popat, Carlos E Bueso-Ramos, Roland L Bassett, Issa F Khouri
In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90-100 days post alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily if tolerated in each patient...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28495641/safety-and-efficacy-of-infliximab-therapy-in-the-setting-of-steroid-refractory-acute-graft-versus-host-disease
#9
Fevzi F Yalniz, Mehrdad Hefazi, Kristen McCollough, Mark R Litzow, William J Hogan, Robert Wolf, Hassan Alkhateeb, Ankit Kansagra, Moussab Damlaj, Mrinal M Patnaik
Acute graft versus host disease (aGVHD) is the leading cause of morbidity and mortality following allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first line treatment; however, less than half of the patients achieve durable remissions. Studies suggest that tumor necrosis factor alpha (TNF-α), a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-tumor necrosis factor alpha (TNF-α) therapy with infliximab in 35 patients with steroid refractory aGVHD (SR-aGVHD)...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28487238/the-recipient-ccr5-variation-predicts-survival-outcomes-after-bone-marrow-transplantation
#10
Tomohiro Horio, Shohei Mizuno, Kaori Uchino, Motonori Mizutani, Ichiro Hanamura, J Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Akiyoshi Takami
The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28486431/mesenchymal-stem-cell-derived-extracellular-vesicles-a-role-in-hematopoietic-transplantation
#11
REVIEW
Luciana De Luca, Stefania Trino, Ilaria Laurenzana, Daniela Lamorte, Antonella Caivano, Luigi Del Vecchio, Pellegrino Musto
Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28484267/microrna-146a-reduces-mhc-ii-expression-via-targeting-jak-stat-signaling-in-dendritic-cells-after-stem-cell-transplantation
#12
N Stickel, K Hanke, D Marschner, G Prinz, M Köhler, W Melchinger, D Pfeifer, A Schmitt-Graeff, T Brummer, A Heine, P Brossart, D Wolf, N von Bubnoff, J Finke, J Duyster, J Ferrara, U Salzer, R Zeiser
Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant-recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a(-/-) dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected-DCs ameliorated disease...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28483716/prophylactic-donor-lymphocyte-infusion-dli-followed-by-minimal-residual-disease-and-graft-versus-host-disease-guided-multiple-dlis-could-improve-outcomes-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-refractory-relapsed-acute-leukemia
#13
Chen-Hua Yan, Qi-Fa Liu, De-Pei Wu, Xi Zhang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, He Huang, Hai Bai, Fen Huang, Xiao Ma, Xiao-Jun Huang
Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD)-test and graft-versus-host disease (GvHD) guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed...
May 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28475513/nodular-sclerodermatous-chronic-cutaneous-graft-versus-host-disease-gvhd-a-new-clinicopathological-variant-of-cutaneous-sclerodermatous-gvhd-resembling-nodular-keloidal-scleroderma
#14
Lucía Prieto-Torres, Francesca Boggio, Alexandra Gruber-Wackernagel, Lorenzo Cerroni
Cutaneous chronic graft-versus-host disease (GvHD) has a broad spectrum of clinicopathological presentations, the most common ones being poikiloderma, lichen planus-like eruptions, lichen sclerosus-like lesions, morphea-like plaques, and deep sclerosis. New forms of chronic cutaneous GvHD with different clinicopathological characteristics have been described, most of them mimicking cutaneous manifestations of autoimmune diseases. We report the case of a 35-year-old man who underwent allogenic stem cell transplantation for a therapy-associated acute myeloid leukemia and developed an acute GvHD with involvement of skin and gastrointestinal tract...
April 25, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28473406/phase-i-multicenter-trial-of-brentuximab-vedotin-for-steroid-refractory-acute-graft-vs-host-disease-gvhd
#15
Yi-Bin Chen, Miguel-Angel Perales, Shuli Li, Maria Kempner, Carol Reynolds, Jami Brown, Yvonne A Efebera, Steven M Devine, Areej El-Jawahri, Steven L McAfee, Thomas R Spitzer, Robert J Soiffer, Jerome Ritz, Corey Cutler
Therapy for steroid-refractory acute GVHD remains suboptimal. Pre-clinical data demonstrate increased CD30 expression on activated CD8(+) T-cells during acute GVHD. Brentuximab vedotin (BV) is an antibody-drug conjugate targeting CD30. We conducted a multicenter phase I trial (ClinicalTrials.gov NCT01940796) in 34 patients to establish the maximum tolerated dose (MTD) of BV for treatment of steroid-refractory acute GVHD. A 3+3 cohort design was conducted initially with BV given weekly x 3 doses followed by maintenance dosing (initial dose 0...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28470889/in-vitro-induction-of-human-regulatory-t-cells-itregs-using-conditions-of-low-tryptophan-plus-kynurenines
#16
K L Hippen, R S O'Connor, A M Lemire, A Saha, E A Hanse, N C Tennis, S C Merkel, A Kelekar, J L Riley, B L Levine, C H June, L S Kean, M L MacMillan, J S Miller, J E Wagner, D H Munn, B R Blazar
Thymic regulatory T cells (tTreg) or induced Tregs (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously we demonstrated that plasmacytoid dendritic cell (pDC) indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (Low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp+Kyn iTreg and tTregs potently suppress Teffector cell proliferation equivalently but are phenotypically distinct...
May 4, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28468799/pd-1-blockade-for-relapsed-lymphoma-post-allogeneic-hematopoietic-cell-transplant-high-response-rate-but-frequent-gvhd
#17
Bradley M Haverkos, Diana Abbott, Mehdi Hamadani, Philippe Armand, Mary E Flowers, Reid Merryman, Manali Kamdar, Abraham Sebastian Kanate, Ayman Saad, Amitkumar Mehta, Siddhartha Ganguly, Timothy S Fenske, Parameswaran Hari, Robert Lowsky, Leslie Andritsos, Madan Jagasia, Asad Bashey, Stacey Brown, Veronika Bachanova, Deborah Stephens, Shin Mineishi, Ryotaro Nakamura, Yi-Bin Chen, Bruce R Blazar, Jonathan Gutman, Steven M Devine
Given the limited treatment options for relapsed lymphoma post allogeneic hematopoietic cell transplantation (allo-HCT) and the success of PD-1 blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label following allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post allo-HCT and prior to anti-PD-1...
May 3, 2017: Blood
https://www.readbyqxmd.com/read/28452054/comparing-outcomes-of-matched-related-donor-and-matched-unrelated-donor-hematopoietic-cell-transplants-in-adults-with-b-cell-acute-lymphoblastic-leukemia
#18
Eric Segal, Michael Martens, Hai-Lin Wang, Ruta Brazauskas, Daniel Weisdorf, Brenda M Sandmaier, H Jean Khoury, Marcos de Lima, Wael Saber
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-matched related donors (RDs) and allogeneic HCT using HLA-matched unrelated donors (URDs) produce similar outcomes for patients with acute myelogenous leukemia, whereas the donor source has been reported to be a predictor of outcomes in myelodysplastic syndrome. METHODS: Post-HCT outcomes for 1458 acute lymphoblastic leukemia patients from 2000 to 2011 were analyzed, and RD and URD transplants were compared...
April 27, 2017: Cancer
https://www.readbyqxmd.com/read/28450387/composite-biomarker-panel-for-prediction-of-severity-and-diagnosis-of-acute-gvhd-with-t-cell-depleted-allogeneic-stem-cell-transplants-single-centre-pilot-study
#19
San San Min, Varun Mehra, Jennifer Clay, Gemma F Cross, Abdel Douiri, Tracy Dew, Tanya N Basu, Victoria Potter, M Mansour Ceesay, Antonio Pagliuca, Roy A Sherwood, Royce P Vincent
AIMS: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT. METHODS: We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD...
April 27, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28447161/prediction-of-graft-versus-host-disease-a-biomarker-panel-based-on-lymphocytes-and-cytokines
#20
Holger Budde, Susanne Papert, Jens-Holger Maas, Holger M Reichardt, Gerald Wulf, Justin Hasenkamp, Joachim Riggert, Tobias J Legler
Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment...
April 26, 2017: Annals of Hematology
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