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Graft vs host disease

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https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#1
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28632323/clinical-outcomes-of-hla-dpb1-mismatches-in-10-10-hla-matched-unrelated-donor-recipient-pairs-undergoing-allogeneic-stem-cell-transplant
#2
Ann M Moyer, Shahrukh K Hashmi, Cynthia M Kroning, Walter K Kremers, Steven R De Goey, Mrinal Patnaik, Mark Litzow, Dennis A Gastineau, William J Hogan, Eapen K Jacob, Justin D Kreuter, Laurie L Wakefield, Manish J Gandhi
OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10)...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28608529/comparison-of-the-cellex%C3%A2-and-uvar-xts%C3%A2-closed-system-extracorporeal-photopheresis-devices-in-the-treatment-of-chronic-graft-versus-host-disease
#3
Robert M Whittle, Helen Denney, Andrew D Chantry, Arun Alfred, Peter C Taylor
Extracorporeal Photopheresis (ECP) is a cellular immunotherapy frequently used for steroid-refractory graft-versus-host disease (GVHD). Chronic GVHD (cGVHD), response to ECP is associated with survival benefit. The UVAR-XTS(TM) system and the more recently developed CELLEX(TM) device (both Therakos(TM) ) are the mainstay for ECP-delivery in the UK and US. No comparison of treatment outcomes has been reported. We retrospectively compared cGVHD response and steroid reduction and withdrawal in patients treated exclusively over 12 months with either the XTS (n = 51) or CELLEX (n = 50)...
June 13, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28607133/loss-of-thymic-innate-lymphoid-cells-leads-to-impaired-thymopoiesis-in-experimental-graft-vs-host-disease
#4
Jarrod A Dudakov, Anna M Mertelsmann, Margaret H O'Connor, Robert R Jenq, Enrico Velardi, Lauren F Young, Odette M Smith, Richard L Boyd, Marcel R M van den Brink, Alan M Hanash
Graft vs. host disease (GVHD) and post-transplant immunodeficiency are frequently related complications of allogeneic hematopoietic transplantation. Alloreactive donor T cells can damage thymic epithelium, thus limiting new T cell development. While the thymus has a remarkable capacity to regenerate after injury, endogenous thymic regeneration is impaired in GVHD. The mechanisms leading to this regenerative failure are largely unknown. Here we demonstrate in experimental mouse models that GVHD results in depletion of intrathymic group 3 innate lymphoid cells (ILC3s) necessary for thymic regeneration...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28602890/posterior-reversible-encephalopathy-syndrome-after-hematopoietic-cell-transplantation-in-children-with-hemoglobinopathies
#5
Javid Gaziev, Simone Marziali, Katia Paciaroni, Antonella Isgrò, Francesca Di Giuliano, Giorgia Rossi, Marco Marziali, Gioia De Angelis, Cecilia Alfieri, Michela Ribersani, Marco Andreani, Maria Giuseppina Palmieri, Fabio Placidi, Andrea Romigi, Francesca Izzi, Roberto Floris, Nicola Biagio Mercuri
Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors (CI) used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n=222, 1.4-17.8 years old) versus sickle cell disease (SCD; n=59, 2-17 years old) who underwent hematopoietic cell transplantation (HCT) from HLA-matched siblings or alternative donors and analyzed the risk factors for PRES. Overall, 31 children developed CI-related PRES (11%), including 30 patients with seizures and 1 patient without seizures...
June 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28588699/irradiation-of-peripheral-blood-mononuclear-cells-with-7-5-gy-x-rays-prior-to-donor-lymphocyte-infusion-inhibits-proliferation-while-preserving-cytotoxicity-and-improves-the-effectiveness-of-hsct-in-patients-with-hematological-malignancies
#6
Yong-Qiu Wei, Xi-Nan Cen, Hui-Hui Liu, Yu-Hua Sun, Yong-Jin Shi, Wei Liu, Yu-Jun Dong, Han-Yun Ren
The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28584210/atopic-dermatitis-like-graft-versus-host-disease-and-lichen-planus-like-graft-versus-host-disease-alterations-in-skin-barrier-function-and-related-molecules
#7
Kun Li, Zhang-Lei Mu, Xue Chen, Guang-Dong Wen, Yan Zhao, Jian-Zhong Zhang
BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms. METHODS: Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28561378/epidemiology-of-bloodstream-infections-after-myeloablative-and-non-myeloablative-allogeneic-hematopoietic-stem-cell-transplantation-a-single-center-cohort-study
#8
Lars I Gjaerde, Claus Moser, Henrik Sengeløv
BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop bloodstream infections (BSI). We aimed to describe the etiologies and antibiotic resistance patterns of BSI after allo-HSCT, and, since knowledge about the impact of conditioning regimen is limited, we looked at the incidence, timing, risk factors, and mortality of BSI separately for myeloablative (MA)- and non-myeloablative (NMA)-conditioned patients. METHODS: All 460 patients (207 MA- and 253 NMA-conditioned) who underwent their first allo-HSCT at our center from 2008 to 2013 were included in a historical cohort...
May 31, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28554856/beneficial-role-of-low-dose-atg-in-unrelated-stem-cell-transplantation-for-adult-patients-with-acquired-severe-aplastic-anemia-reduction-of-graft-versus-host-disease-gvhd-and-improvement-of-gvhd-free-failure-free-survival-rate
#9
Sung-Soo Park, Dae Hun Kwak, Young-Woo Jeon, Jae-Ho Yoon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Woo-Sung Min, Jong Wook Lee
Stem cell transplantation from an unrelated donor (URD SCT) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introduction of antithymocyte globulin (ATG) to the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA...
May 26, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28552421/reduced-intensity-conditioning-with-busulfan-fludarabine-and-antithymocyte-globulin-for-hematopoietic-cell-transplantation-from-unrelated-or-haploidentical-family-donors-in-patients-with-acute-myeloid-leukemia-in-remission
#10
Kyoo-Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Han-Seung Park, Eun-Ji Choi, Sun-Hye Ko, Miee Seol, Young-Shin Lee, Young-A Kang, Mijin Jeon, Seunghyun Baek, You-Lee Kang, Sung-Han Kim, Sung-Cheol Yun, Hawk Kim, Jae-Cheol Jo, Yunsuk Choi, Young-Don Joo, Sung-Nam Lim
To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4...
May 25, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#11
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naïve and central memory T-cell populations, and activation of resting T-cells resulted in its decreased expression...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#12
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28542105/national-trends-and-in-hospital-outcomes-of-patients-with-solid-organ-transplant-undergoing-spinal-fusion
#13
Hiroyuki Yoshihara, Daisuke Yoneoka, Carl Paulino, Sanjeev Agarwal, Jose R Reyna, Kazuhiro Hasegawa
STUDY DESIGN: A retrospective analysis of population-based national hospital discharge data collected for the Nationwide Inpatient Sample (NIS) OBJECTIVES.: To examine the demographics and in-hospital outcomes of patients with solid organ transplant (SOT) undergoing spinal fusion on a national level SUMMARY OF BACKGROUND DATA.: Solid organ transplantation has become more common in recent years and some of these patients undergo spinal fusion surgery. However, there is little information regarding the trends and outcomes in such patients...
May 25, 2017: Spine
https://www.readbyqxmd.com/read/28536366/advances-in-the-use-of-regulatory-t-cells-for-the-prevention-and-therapy-of-graft-vs-host-disease
#14
REVIEW
Reshma Ramlal, Gerhard C Hildebrandt
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product...
May 16, 2017: Biomedicines
https://www.readbyqxmd.com/read/28499937/haploidentical-allogeneic-hematopoietic-cell-transplantation-for-multiple-myeloma-using-post-transplantation-cyclophosphamide-graft-versus-host-disease-prophylaxis
#15
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 (allo) hematopoietic cell transplantation (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 are little available data regarding this treatment. We analyzed survival outcomes of 30 heavily pretreated MM patients who received haplo-HCT with post-transplantation cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis...
May 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28494062/conjunctival-lesion-in-a-patient-with-ocular-graft-vs-host-disease
#16
Grace L Paley, Asim V Farooq, Anthony J Lubniewski
No abstract text is available yet for this article.
May 11, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28473406/phase-i-multicenter-trial-of-brentuximab-vedotin-for-steroid-refractory-acute-graft-vs-host-disease-gvhd
#17
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/28466469/recipient-donor-kir-ligand-matching-prevents-cmv-reactivation-post-haploidentical-t-cell-replete-transplantation
#18
Xiang-Yu Zhao, Xue-Yi Luo, Xing-Xing Yu, Xiao-Su Zhao, Ting-Ting Han, Ying-Jun Chang, Ming-Rui Huo, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Dan Li, Zheng-Fan Jiang, Xiao-Jun Huang
Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28460445/autoimmune-hematological-diseases-following-haploidentical-donor-hematopoietic-stem-cell-transplant-compared-with-matched-sibling-and-unrelated-donor
#19
Weiran Lv, Zhiping Fan, Fen Huang, Na Xu, Li Xuan, GuopanYu, Qianli Jiang, Hongsheng Zhou, Ren Lin, Xin Zhang, Jing Sun, Qifa Liu
Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. This study was to analyze the incidence and risk factors of AHDs as well as their response to treatment . Four hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 124 haploidentical donor (HRD), 140 unrelated donor (MUD) and 181 HLA-matched sibling donor (MSD) transplants...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446306/-relationship-between-nk-cell-reconstitution-and-agvhd-after-allo-hsct
#20
Lu-Lu Wan, Jian-Lin Chen, Chen Xu, Bo-Tao Li, Jiang-Wei Hu, Xiao Lou, Fan Yang, Na Liu, Yong-Feng Su, San-Chun Lan, Qing-Han Wang, Zhuo-Qing Qiao, Lei Wang, Min Jiang, Yu-Hang Li, Liang-Ding Hu
OBJECTIVE: To investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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