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https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#1
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29346409/prediction-of-absolute-risk-of-acute-graft-versus-host-disease-following-hematopoietic-cell-transplantation
#2
Catherine Lee, Sebastien Haneuse, Hai-Lin Wang, Sherri Rose, Stephen R Spellman, Michael Verneris, Katharine C Hsu, Katharina Fleischhauer, Stephanie J Lee, Reza Abdi
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials...
2018: PloS One
https://www.readbyqxmd.com/read/29344728/-cutaneous-graft-versus-host-disease
#3
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/29339271/early-increase-in-complement-terminal-pathway-activation-marker-sc5b-9-is-predictive-for-the-development-of-thrombotic-microangiopathy-after-stem-cell-transplantation
#4
Orsolya Horváth, Krisztián Kállay, Dorottya Csuka, Blanka Mező, György Sinkovits, Csaba Kassa, Anita Stréhn, Katalin Csordás, János Sinkó, Zoltán Prohászka, Gergely Kriván
Hematopoietic stem cell transplantation- (HSCT-) associated thrombotic microangiopathy (TA-TMA) is a multifactorial complication, and its prediction is largely unresolved.Our aim was to analyze changes of complement profile after HSCT in order to identify potential markers of TA-TMA development. Thirty- three consecutive pediatric patients (9.6 ± 4.4 years old) were included in this study who underwent allogeneic HSCT due to malignant (n=17) or non malignant (n=16) indications. Graft versus host disease (GVHD) was diagnosed using Glucksberg criteria, viral reactivation was monitored, five different TA-TMA diagnostic criteria were applied and all important clinical and laboratory parameters of TA-TMA activity were registered...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematological-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#5
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematological malignancies are poor. Sequential strategies have shown promising results in refractory acute myeloid leukemia (AML), but have not been validated in a haploidentical (Haplo) setting. We developed a new sequential approach combining chemotherapy with broad anti-tumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, cyclophosphamide 1600 mg/m2 from Day-15 to -10), followed after 3 days of rest by reduced-intensity conditioning regimen (fludarabine 150 mg/m2, intravenous busulfan 6...
January 11, 2018: Biology of Blood and 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
#6
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
#7
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/29330757/-myelodysplastic-syndrome-acute-leukemia-and-stem-cell-transplantation
#8
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/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
#9
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
#10
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/29330269/central-nervous-system-graft-versus-host-disease-cns-gvhd-after-allogeneic-haematopoietic-stem-cell-transplantation
#11
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/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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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/29296834/haploidentical-transplant-in-patients-with-myelodysplastic-syndrome
#18
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
#19
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
#20
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
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