TY - JOUR. T1 - Recipient and donor JAK2 46/1 haplotypes are associated with acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. AU - Balassa, Katalin. AU - Krahling, Tunde. AU - Remenyi, Peter. AU - Batai, Arpad. AU - Bors, Andras. AU - Kiss, Katalin Piroska. AU - Torbagyi, Eva. AU - Gopcsa, Laszlo. AU - Lengyel, Lilla. AU - Barta, Aniko. AU - Varga, Gergely. AU - Tordai, A.. AU - Masszi, T.. AU - Andrikovics, H.. PY - 2016/7/7. Y1 - 2016/7/7. N2 - Several genetic polymorphisms have been implicated to affect the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of cytokines in acute graft-versus-host disease (aGvHD) is well established and many of the involved cytokines signal through the Janus kinase (JAK) pathways. In this study, we assessed the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 acute myeloid leukemia patients. Both, recipient and donor 46/1 haplotypes ...

TY - JOUR. T1 - Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. AU - Svegliati, Silvia. AU - Olivieri, Attilio. AU - Campelli, Nadia. AU - Luchetti, Michele. AU - Poloni, Antonella. AU - Trappolini, Silvia. AU - Moroncini, Gianluca. AU - Bacigalupo, Andrea. AU - Leoni, Pietro. AU - Avvedimento, Enrico V.. AU - Gabrielli, Armando. PY - 2007/7/1. Y1 - 2007/7/1. N2 - Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (PDGF) receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoantibodies are also present in patients affected by ecGVHD. Serum from 39 patients subjected to allogeneic stem cell transplantation for hematologic malignancies (22 with ecGVHD and 17 ...

Flowers, ME, Inamoto, Y, Carpenter, PA. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. . vol. 117. 2011. pp. 3214-9. (Multiple studies in the 1990s evaluated risk factors for acute GVHD. This recently published large study from a single center confirmed and extended prior observations. Of note, recipient age was not a statistically significant risk in this study.). Jagasia, M, Arora, M, Flowers, ME. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. vol. 119. 2012. pp. 296-307. (Analysis of over 5000 related and unrelated donor transplants defined risk factors for acute GVHD.). Rühl, H, Bein, G, Sachs, UJ. Transfusion-associated graft-versus-host disease. . vol. 23. 2009. pp. 62-71. (Excellent review of settings in which GVHD can develop, other than allogeneic bone marrow transplantation.). Ferrara, JL, Levine, JE, ...

This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patients immune system reject the donors stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the bodys normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening ...

Abstract. Background: Acute graft-versus-host disease (GvHD) is mediated by activated T lymphocytes. Alemtuzumab is an unconjugated, humanized IgG1 kappa monoc

Chronic graft-versus-host disease (GvHD) has become a leading cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT) and can burden patients with devastating and lifelong health effects. Our understanding of the pathogenic mechanisms underlying chronic GvHD remains incomplete and this lack of understanding is reflected by lack of clear therapeutic approaches to steroid refractory disease. Observations predominantly from mouse models and human correlative studies currently support a three phase model for the initiation and development of chronic GvHD: 1) early inflammation and tissue damage triggers the innate immune system. This leads to inflammatory cytokine/chemokine patterns that recruit effector immune cell populations; 2) chronic inflammation causes the loss of central and peripheral tolerance mechanisms leading to emergence of pathogenic B and T cell populations that promote autoimmune and alloimmune reactions; 3) the dysregulated immunity causes

A Single-Cohort, Phase 2 Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease - The purpose of this study is to assess the efficacy of ruxolitinib in combination with corticosteroids in subjects with Grades II to IV steroid-refractory acute graft-versus-host disease (GVHD).

Obesity is a form of chronic inflammation, termed meta-inflammation, resulting in the development of many chronic diseases such as diabetes and cancer. In this study, we assessed the impact of obesity on recipient graft-versus-host disease (GVHD) outcome post allogeneic HSCT using mouse models. In a model of sclerodermatous chronic GVHD, lean or diet-induced obese (DIO) BALB/c mice received 800 cGy total body irradiation (TBI), bone marrow cells, and splenocytes from H2-identical but minor MHC-mismatched B10.D2 mice. To mimic major MHC mismatch transplant which results in acute GVHD impacting gut, skin and liver, lean or DIO C57BL/6 mice received 1050 cGy TBI, bone marrow cells, and different doses of purified T cells from BALB/c mice. Strikingly, after the minor mismatch HSCT, all DIO mice succumbed to gut pathology while all lean mice survived and developed sclerodermatous GVHD at week 3 post transplant. In both models, pathological assessment indicated marked gut pathology in DIO mice ...

TY - JOUR. T1 - Acute graft-versus-host disease of the heart. AU - Roberts, Stephen S.. AU - Leeborg, Nicky. AU - Loriaux, Marc. AU - Johnson, F. Leonard. AU - Huang, Meei Li. AU - Stenzel, Peter. AU - Thiede, Christian. AU - Godder, Kamar T.. PY - 2006/10/15. Y1 - 2006/10/15. N2 - Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality after bone marrow transplantation. Acute GVHD most commonly involves the skin, gastrointestinal tract, and liver. Involvement of other organ systems is rare and remains controversial. We report a patient with GVHD who suffered a fatal ventricular arrhythmia shortly after bone marrow transplantation. Autopsy of the heart showed lymphocyte infiltration. Investigations for cardiotrophic viruses were negative, and chimerism analysis of the heart showed both donor and recipient DNA. We conclude that the cause of death was possibly graft-versus-host disease of the heart. A review of the literature revealed a total of 14 cases of possible cardiac ...

Important dosing information for Jakafi for steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years of age and older.

PRIMARY OBJECTIVES:. I. To determine whether the incidence of acute GVHD grades II-IV can be reduced to less than the historical rate of 70% with the triple-immunosuppressant combination of cyclosporine (CSP)/mycophenolate mofetil (MMF) with sirolimus in human leukocyte antigens (HLA) class I or class II mismatched related or unrelated donor hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning. The evaluation will be carried out separately among class I and class II mismatched patients.. SECONDARY OBJECTIVES:. I. To evaluate the incidence of non-relapse mortality before day 100.. II. To evaluate the incidences of grades III-IV acute GVHD.. OUTLINE:. CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2. Patients also undergo total-body irradiation on day 0.. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation.. IMMUNOSUPPRESSION: Patients receive sirolimus orally (PO) once daily (QD) on ...

Microsatellite polymorphism (CA)n within the first intron of the interferon- gamma gene was assessed in 160 recipients of an allogeneic hematopoietic stem cell transplant (HSCT). IFN- gamma 3/3 was found to be associated with an increased risk of chronic graft-versus-host disease (GvHD) (11/27 vs 26/133, p=0.02). Forward logistic regression analysis confirmed the role of IFN-gamma 3/3 genotype as one of the risk factors for manifestation of chronic GvHD (OR=3.180, p=0.018) together with previous acute GvHD (OR=2.752, p=0.024), cyclosporine A monotherapy (OR=2.607, p=0.029) and malignant disorders (OR=4.371, p=0.032).. ...

Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system, can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, ELISA and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B and NK-cell lineages that

Helper T-lymphocyte precursor (HTLp) frequency from 19 allogeneic bone marrow donors was tested to detect weak antigenic differences with the recipient, and then compared to the outcome. HTLp frequency was estimated in limiting dilution cultures, and HLA-DR and CD 80 expression by stimulating cells was measured by flow cytometry. 12/19 patients experienced acute graft-versus-host disease (aGVHD) grade II-IV. A good correlation was found between high pretransplant HTLp frequency and grade II-IV aGVHD (median: 1/55848 PBMNC for II-IV GVHD versus 1/184346 for 0-I GVHD; P = 0.008). Sensitivity was 82%, specificity 63%, negative predictive value 71% and positive predictive value 75%. Long-term survivors also had a lower HTLp median frequency (1/143354) when compared with patients who died as a result of the transplant procedure (1/22100, P , 0.001). No correlation was found between HTLp frequency and HLA-DR or CD80 expression by patients cells. We conclude that HTLp frequency estimation can predict, ...

Clinical trial for Hematopoietic Stem Cell Transplantation | Multiple Myeloma , Ixazomib in the Prophylaxis of Chronic Graft-versus-host Disease.

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow-derived T cells do not mediate severe GVHD because of their quantity and/or phenotype. During the course of experiments testing the impact of housing temperatures on GVHD, we discovered that this apparent resistance is a function of the relatively cool ambient housing temperature. Murine bone marrow-derived T cells have the ability to mediate severe GVHD in mice housed at a thermoneutral temperature. Specifically, mice housed at Institutional Animal Care and Use Committee-mandated, cool standard temperatures (∼22°C) are more resistant to developing GVHD than are mice housed at thermoneutral temperatures (∼30°C). We learned that the mechanism underlying this housing-dependent immunosuppression is associated with increased norepinephrine production and excessive signaling through ...

TY - JOUR. T1 - Pathophysiologic mechanisms of acute graft-vs.-host disease. AU - Ferrara, James L M. AU - Levy, Robert B. AU - Chao, Nelson J.. PY - 1999/12/1. Y1 - 1999/12/1. N2 - Graft-vs.-host disease (GVHD) remains the major toxicity of allogeneic bone marrow transplantation. Mechanistic studies in experimental animal models provide a better understanding of the complex relationships and cascade of events mediated by cellular and inflammatory factors. Also, advances in basic immunology have cleared the way for a more precise view of allogeneic reactions between donor and host. In addition, the use of mutant mice lacking critical cytolytic proteins has helped map out the molecular pathways by which GVHD targets organ damage. In this article, these mechanisms are reviewed and synthesized into a coherent conceptual framework, providing a state-of-the-art summary of the pathophysiology of acute GVHD.. AB - Graft-vs.-host disease (GVHD) remains the major toxicity of allogeneic bone marrow ...

Graft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute GvHD (aGvHD) is seen after alloHSCT and the incidence of aGvHD is around 30%-50%. aGvHD prophylaxis is essential in patients undergoing allo-HSCT. Initial therapy for aGvHD is steroids. Prognosis is poor in aGvHD patients not responding to steroids. In this article, the pathobiology, clinical findings, prophylaxis, and treatment of aGvHD will be summarized.. Keywords: Graft-versus-host disease, Acute, ...

Background: Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant, resulting from the donors immune cells at

Average onset of chronic graft-versus-host disease (cGVHD)was 8.2±4 months in Scl-GVHD and 6.7±4 in non-Scl-cGVHD. Average Modified Rodnan Skin Score was 8.2 in Scl-GVHD, 12 in SSc and 0 in non-Scl-GVHD. Histopathological analysis of Scl-GVHD confirmed full thickness skin fibrosis in the presence of a more dense tissue infiltrate and the absence of the fibroproliferative vasculopathy and vessel rarefication peculiar of SSc. On the contrary non-Scl-GVHD showed intense tissue infiltrate and neither tissue fibrosis nor fibroproliferative vasculopathy. AIF-1 expression was significantly increased in both Scl- and non-Scl-cGVHD. The pattern of expression was mostly in perivascular and tissue infiltrating mononuclear cells, whereas microvascular endothelial cells (MVECs) did not show any AIF-1 expression despite what has been previously shown in SSc. Cav-1 expression was profoundly decreased in both SSc and Scl-GVHD whereas it was conserved in non-Scl-GVHD.. ...

Definition of related HLA-identical donor in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is related HLA-identical donor? Meaning of related HLA-identical donor as a legal term. What does related HLA-identical donor mean in law?

Лечение интерлейкином-2 рефрактерной хронической реакции трансплантат-против-хозяинаTreatment of refractory chronic graft-versus-host disease with interleukin-2

There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone d

FDA Grants Breakthrough Therapy Designations to Two Therapies for Acute and Chronic Graft-Versus-Host Disease - Latest & Greatest, News - ASH Clinical News

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Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating (Ki67+) and producing the proinflammatory cytokines IFN-γ and IL-17 in situ. Comparatively, the majority ...

This phase I study was conducted to evaluate hCG/EGF in patients with Minnesota High Risk and steroid dependent or refractory acute graft-versus-host disease (aGvHD)

Restoration of chronic graft vs host disease (Cgvhd)-induced autoantibody (autoAb) by human granulocyte-colony stimulation factor (huG-CSF) correlates with CD4+

TY - JOUR. T1 - Sirolimus-containing graft-versus-host disease prophylaxis in patients with lymphoma. AU - Mehta, Jayesh. PY - 2009/10/1. Y1 - 2009/10/1. UR - http://www.scopus.com/inward/record.url?scp=70350461744&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=70350461744&partnerID=8YFLogxK. U2 - 10.1200/JCO.2009.23.9483. DO - 10.1200/JCO.2009.23.9483. M3 - Letter. C2 - 19720890. AN - SCOPUS:70350461744. VL - 27. SP - e138. JO - Journal of Clinical Oncology. JF - Journal of Clinical Oncology. SN - 0732-183X. IS - 28. ER - ...

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) patients. The median time from transplant to onset of ...

A 45-year-old man received growth factor-mobilized blood cells from an HLA-matched unrelated male donor after conditioning with 12 Gy total body irradiation and cyclophosphamide for treatment of acute myeloid leukemia with persistent disease. He received methotrexate and tacrolimus for immunosuppression after HCT. He developed acute GVHD of the skin and gut, which resolved after treatment with steroid cream and oral beclomethasone and budesonide. Because malignant cells persisted after HCT, treatment was administered with azacytidine, and immunosuppression with tacrolimus was withdrawn by day 100, 3 months earlier than originally planned.. Malignant cells disappeared, but 7 months after HCT and 2 months after the third cycle of azacytidine, he was diagnosed with severe chronic GVHD (NIH global score). Affected sites included the skin (erythematous rash involving ,50% body surface area [BSA]), mouth (ulcers and lichenoid features), fasciae (wrist tightness and leg edema), liver (alanine ...

AIM: In this study, 58 paediatric patients were prospectively evaluated with a number of screening studies performed between 0 and 180 days after allogenic hematopoietic stem cells transplantation (HSTC) to detect any risk factors for developing oral manifestations of acute Graft-versus-Host Disease (a-GvHD). MATERIALS AND METHODS: A total of 58 paediatric allogenic HSTC patients (37 males aged 1 to 15, and 21 females aged 4 to 18), entered the study and were observed by a trained dental team for a period of 6 months following transplantation while assuming cyclosporine, an immunosuppressive agent with a-GvHD prophylactic activity. Mean age at transplantation was 7.2 years old. Screening studies included physical examination, complete blood counts and liver function tests. Complete extraoral and intraoral clinical examinations were performed for all patients to detect oral lesions. Furthermore, some variables (sex, number of HSTC performed in the same patient, degree of HLA disparity and the ...

Graft versus host disease (GVHD) is a lethal complication after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells are the main cause and driver of GVHD pathobiology. However, these cells are also beneficial as they have an anti-tumor effect. The current standard to prevent GVHD is to use agents that broadly suppress T cells function, which might result in diminishing T cells anti-tumor effects. Targeting donor T cell trafficking without altering T cell function is a potential solution and has been shown to be effective in experimental GVHD mouse models1-3. Integrins play a major role in T cell trafficking to inflamed tissues. Many investigators including our group found that different types of integrins play an integral role in GVHD pathology (reviewed in reference number 4). In this paper we showed for the first time that genetic deletion of α4 integrin in donor T cells that were isolated from the spleens of B6 donor mice and transplanted into fully mismatched BALB/C ...

David A. Jacobsohn, MD, ScM, Chief of the Blood and Marrow Transplantation Division at Childrens National Medical Center, is the lead author on the first, prospective, longitudinal study that concludes with recommendations in evaluating skin response in chronic graft-versus-host disease (GVHD).

A new monoclonal rat anti-human lymphocyte antibody (CAMPATH-1) which lyses cells with autologous human complement was used for depletion of T lymphocytes from human bone-marrow allografts in vitro before transplantation in 11 high-risk patients. HLA-matched siblings were used as marrow donors. T-cell depletion was substantial when measured by E-rosette formation (0-0.18% residual T cells) and immunofluorescence with a monoclonal anti-T-cell antibody (0-0.5%). No anti-graft-versus-host disease prophylaxis was given after transplantation. Rapid engraftment was reported in all patients, and the post-transplantation course was uneventful. No signs of graft-versus-host disease developed in any of the patients, who were observed for a maximum period of 12 months. The method might be suitable for larger-scale studies in high-risk patients. The late graft failure seen in 2 patients may reflect residual host resistance uncompromised by GvHD.

Геморрагический энтерит, ассоциированный с парвовирусом В19 после трансплантации гемопоэтических стволовых клеток: клинический случай и данные литературыHaemorrhagic enteritis associated with parvovirus B19 following hematopoietic stem cell transplantation: a case report and literature data

TY - JOUR. T1 - More immune dysregulation. T2 - Sarcoidosis and chronic graft-versus-host disease after allogeneic stem cell transplant. AU - Manalo, Iviensan F.. AU - Miller, India Ashton. AU - Davis, Loretta S. PY - 2016/3/1. Y1 - 2016/3/1. KW - Allogeneic hematopoietic stem cell transplant. KW - Chronic graft-versus-host disease. KW - Cutaneous manifestations of systemic disease. KW - Cutaneous sarcoidosis. KW - Graft-versus-host-disease. KW - Granulomatous dermatitis. KW - Human leukocyte antigen. KW - Noncaseating granulomas. KW - Sarcoidosis. UR - http://www.scopus.com/inward/record.url?scp=84960876408&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84960876408&partnerID=8YFLogxK. U2 - 10.1016/j.jdcr.2016.01.008. DO - 10.1016/j.jdcr.2016.01.008. M3 - Article. AN - SCOPUS:84960876408. VL - 2. SP - 138. EP - 140. JO - JAAD Case Reports. JF - JAAD Case Reports. SN - 2352-5126. IS - 2. ER - ...

Reduced intensity conditioning (RIC) regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients and up to 2 years for 311 patients who underwent a RIC HCT at two institutions from January 2008 to December 2010. Multiple linear regression was used to analyze the association between clinical variables, center effect, and costs. Patient and transplant characteristics were comparable between the sites, although differences were seen in pretransplant performance scores. Significant predictors for lower costs for the first 100 days included a diagnosis of lymphoma/myeloma and use of human leukocyte antigen-matched related donors. Grade II-IV acute graft-versus-host disease (GVHD) was associated with higher costs. The overall short-term costs between the two institutions were comparable when adjusted for clinical variables (p = .43). Late costs ...

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Posaconazole (PCZ) is the latest triazole antifungal agent that has been approved for prophylaxis of invasive aspergillosis in high-risk immunocompromised patients, such as allogeneic hematopoietic stem cell transplantation patients, who develop graft-versus-host disease (GVHD). PCZ has high interindividual variability with regard to its plasma trough concentrations (C(min)). Moreover the concentration-efficiency relationship remains to be better characterized in prophylaxis. To determine the variability factors in plasma concentrations, PCZ C(min) and clinical parameters (localization of GVHD, presence of diarrhea, and diagnosis of invasive aspergillosis) were collected retrospectively in 29 consecutive allogeneic hematopoietic stem cell transplantation patients who developed GVHD and were receiving prophylactic PCZ (200 mg 3 times/day ≥ 7 days). Blood samples were analyzed at steady state to determine PCZ C(min) by liquid chromatography-tandem mass spectrometry. The average PCZ C(min) value ...

Results from a phase II clinical trial presented by Kean et al at the 59th American Society of Hematology (ASH) Annual Meeting (Abstract 212) show that the drug abatacept (Orencia) nearly eliminated life-threatening severe acute graft-versus-host disease (GVHD) in patients receiving hematopoietic stem cell transplants.. When added to the standard drug regimen used to prevent GVHD, abatacept reduced the occurrence of acute, grade III-IV GVHD from 32% to 3% in pediatric and adult patients who underwent mismatched unrelated donor stem cell transplants to treat advanced cancer and other blood disorders. As a result, patients receiving the post-transplant regimen with abatacept experienced improved disease-free and overall survival compared to those who did not.. Acute GVHD is a complication that can arise after stem cell transplantation. GVHD occurs when the donated T cells launch a vigorous attack on a patients organs, including the skin, liver, kidneys, lung, and the gastrointestinal tract. For ...

In two situations, transfer of normal unsensitized bone marrow cells into heavily irradiated H-2-identical allogeneic mice caused a high incidence of lethal chronic graft-versus-host disease (GVHD), i.e. mortality occuring between days of 20 and 80 postirradiation. Minor histocompatibility determinants appeared to be the main target for eliciting GVHD. Removing mature T cells from the marrow with anti-Thy 1.2 serum and complement before injection prevented GVHD. On the basis of adding purified T cells to T-cell-depleted marrow cells, it was concluded that contamination of the marrow with as few as 0.3% T cells was sufficient to cause a high incidence of lethal GVHD in certain situations. No GVHD was found with the injection of non-T cells (Thy 1.2-negative cells) or with tolerant T cells. Irradiated recipients of T-cell-depleted marrow cells remained in good health for prolonged periods. These mice showed extensive chimerism with respect to the donor marrow, normal numbers of T and B cells and ...

We discuss clinical strategies for the prophylaxis and treatment of both acute and chronic graft-versus-host disease (GVHD) with particular attention to children. Grades II to IV acute GVHD occur in 10 to 50% of patients given an allogeneic transplantation of haemopoietic stem cells (HSCT) from a genotypically HLA-identical donor. A significantly higher incidence and severity of the disease is reported in patients receiving transplants from partially matched family donors or unrelated volunteers. Younger individuals or patients receiving HSCT from younger donors develop GVHD less frequently than do older recipients. Severe acute GVHD is characterised by a significant decrease in survival probability, even though the graft-versus-leukaemia activity associated with both acute and chronic GVHD may reduce the risk of leukaemia relapse. Prophylaxis of acute GVHD usually consists of in vivo post-grafting immunosuppression with cyclosporin alone or in combination with methotrexate; methotrexate alone ...

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Acute graft-versus-host disease (GVHD) represents a severe, T cell-driven inflammatory complication following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD often affects the intestine and is associated with a poor prognosis. Although frequently detectable, proinflammatory mechanisms exerted by intestinal tissue-infiltrating Th cell subsets remain to be fully elucidated. Here, we show that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal GVHD tissues. Studies in complete MHC-mismatched and minor histocompatibility-mismatched (miHA-mismatched) GVHD models revealed that BATF-expressing T cells were functionally indispensable for intestinal GVHD manifestation. Mechanistically, BATF controlled the formation of colon-infiltrating, IL-7 receptor-positive (IL-7R+), granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+), donor T effector memory (Tem) cells. This T cell ...

TY - JOUR. T1 - A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation. T2 - A Phase II Trial. AU - Koreth, John. AU - Kim, Haesook T.. AU - Lange, Paulina B.. AU - Bindra, Bhavjot. AU - Reynolds, Carol G.. AU - Chammas, Marie J.. AU - Armand, Philippe. AU - Cutler, Corey S.. AU - Ho, Vincent T.. AU - Glotzbecker, Brett. AU - Nikiforow, Sarah. AU - Ritz, Jerome. AU - Blazar, Bruce R.. AU - Soiffer, Robert J.. AU - Antin, Joseph H.. AU - Alyea, Edwin P.. N1 - Funding Information: Financial disclosure: This study was supported in part by Millennium Pharmaceuticals Inc. and Otsuka Pharmaceuticals Inc. , the Jock and Bunny Adams Education and Research Endowment , and by the National Institutes of Health (grants CA183560 , CA183559 , and P01CA142106 ). Publisher Copyright: © 2015 American Society for Blood and Marrow Transplantation. Copyright: Copyright 2015 Elsevier B.V., All rights ...

Abstract In a phase I/II study, the combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) was investigated as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and hematopoietic cell transplantation from an HLA-matched sibling donor. In phase I, 3 groups, each with 10 or 11 patients, received MMF (15 mg/kg) from day 0 to day 27 at decreasing dose intervals of every 12, 8, and 6 hours to determine a safe and effective total daily dose. At the 45 mg/kg/d dosage level, 4 of 11 patients developed only grade II GVHD, and a concentration at steady state of mycophenolic acid (the active moiety of MMF) consistent with a therapeutic range described for solid-organ transplantation was achieved. There was a suggestion of increased toxicity without improved efficacy at the 60 mg/kg/d dosage level. Accordingly, the 45 mg/kg/d dosage was therefore selected for phase II, and another 15 patients were added to this group from the phase I study (n=26). The concentrations at ...

TY - JOUR. T1 - Pharmacokinetics of Basiliximab for the Prevention of Graft-versus-Host Disease in Patients Undergoing Hematopoietic Cell Transplantation with Minimal-Intensity Cyclophosphamide and Fludarabine. AU - Podichetty, Jagdeep T.. AU - Brinda, Bryan J.. AU - Nelson, Robert P.. AU - Karr, Alissa H.. AU - Prasad, Nagendra K.. AU - Quinney, Sara. AU - Foxworthy Scott, Susanna. AU - Kiel, Patrick J.. PY - 2020/1/1. Y1 - 2020/1/1. N2 - Study Objective: Basiliximab is an immunosuppressive monoclonal antibody used for rejection prevention following solid organ transplantation; the pharmacokinetics (PK) of basiliximab in this setting are known. Basiliximab may also be used for prophylaxis and treatment of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT); however, the PK of basiliximab in this setting are not known. Clinical transplant providers expect variation in the volume of distribution and clearance after nonmyeloablative ...

Graft vs. Host disease (GVHD) often occurs after allogeneic bone marrow transplants (BMT). In GVHD, the donors bone marrow attacks the patients organs and tissues, making them less able to function well.

Results:. For the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15 years. The leading causes of death were disease recurrence (21 patients), chronic graft-versus-host disease with complicating infections and lung disease (11 patients), secondary cancer (8 patients), and the acquired immunodeficiency syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded, late death was associated with chronic graft-versus-host disease (P , 0.001), occurrence of secondary cancer (P , 0.001), male sex of the patient (P = 0.05), and female sex of the donor (P = 0.002). Clinical performance was normal (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of patients; 89% of patients resumed full-time work or school. Reduced performance status and incomplete resumption of social activity were associated with chronic graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ dysfunction, and neurologic or psychological problems. ...

Soderberg et al. demonstrated anti-CD13 antibodies in 15/33 bone marrow transplant patients, all of whom developed antibodies at the time of CMV reactivation or disease. CD13 is the known receptor for CMV entry into host cells. When the virus reactivates, it incorporates CD13 into the virion envelope, becoming immunogenic and resulting in antibody production [101, 102]. More recently, soluble CD13 has been shown to be a robust marker for cGVHD in children [88]. Recently, a strong association with a recipient NOD2/CARD15 variant associated with decreased TLR2/4 signaling polymorphisms has strongly correlated with bronchiolitis obliterans secondary to cGVHD [103]. Predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings. N Engl J Med. 1992;327:1613-1617. Schwarer AP, Jiang YZ, Brookes PA, et al. Frequency of antirecipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bonemarrow ...

Tissue antigens, 2007; 69 Suppl 1 doi:10.1111/j.1399-0039.2006.759_4.x. Authors: Shaw B E, Gooley T, Madrigal J A, Malkki M, Marsh S G E Shaw B E, Gooley T, Madrigal J A, Malkki M, Marsh S G E, Petersdorf E W et al.(1) Affiliation: Nottingham City Hospital, Nottingham, United Kingdom Abstract: There is increasing evidence for a significant effect of human leukocyte antigen (HLA)-DPB1 mismatching on complications following unrelated donor haematopoietic cell transplantation (HCT). In this analysis of 5930 patient/donor pairs, we found that a DPB1 mismatch predicted significantly for an increased risk of acute graft-vs-host disease [hazard ratio (HR): 1.33; P-value ...

TY - JOUR. T1 - Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia?. AU - Ringdén, O.. AU - Labopin, M.. AU - Gorin, N. C.. AU - Schmitz, N.. AU - Schaefer, U. W.. AU - Prentice, H. G.. AU - Bergmann, L.. AU - Jouet, J. P.. AU - Mandelli, F.. AU - Blaise, D.. AU - Fouillard, L.. AU - Frassoni, F.. PY - 2000. Y1 - 2000. N2 - During a 13-year period, 5200 autografts, 1039 HLA-identical sibling transplants without acute or chronic graft-vs.-host disease (GVHD) and 67 twins were reported to the European Group for Blood and Marrow Transplantation EBMT. Follow-up time was a median of 32 months. Diagnoses were acute myeloid leukaemia (AML, 4521) and acute lymphoblastic leukaemia (ALL, 1785) in first complete remission. The probability of relapse at 5 years was 51 ± 1% in the autografts, 45 ± 8% in the twins and 34 ± 2% among the HLA-identical siblings (auto vs. sibs, P ,0.0001). In multivariate ...

Hematopoietic stem cell transplantation (HSCT) has become an accepted and widely used treatment option for defined malignant and nonmalignant diseases. Initially, given the considerable transplant-related mortality (TRM), which was partly associated with myeloablative conditioning (MAC), HSCT was restricted to younger patients. However, the introduction of reduced intensity conditioning has increased the proportion of HSCT-eligible patients. Today, approximately 20,000 allogeneic HSCT procedures are performed annually worldwide [1]. Despite improvements in HSCT practices and reductions in TRM, one-third of patients will die without preceding relapse [2]. Besides infection, graft versus host disease (GvHD) remains the main cause of morbidity and mortality after allogeneic HSCT. GvHD is mediated by alloreactive donor lymphocytes that reside in the graft and target nonmalignant host tissues. However, this alloreactivity not only has negative effects but also mediates graft versus tumor (GvT) ...

Meeting Details:. The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform. On August 13, 2020, the committee will discuss biologics license application (BLA) 125706, for remestemcel-L (ex-vivo culture-expanded adult human mesenchymal stromal cells suspension for intravenous infusion), submitted by Mesoblast, Inc. The proposed indication (use) for this product is for the treatment of steroid-refractory acute graft-versus-host disease in pediatric patients. The morning session will discuss issues related to the characterization and critical quality attributes of remestemcel-L as they relate to clinical effectiveness. The afternoon session will discuss results from clinical trials included in BLA 125706.. ...

We have developed an improved porphyrin precursor based method for extracorporeal photopheresis (ECP), for treatment of cutaneous T-cell lymphoma (CTCL), graft versus host disease (GvHD), transplant rejection and other selected autoimmune diseases.

GVHD can be acute or chronic. Patients may experience none, one or both types. Acute GVHD occurs within the first 100 days or so following allogeneic BMT, and chronic GVHD occurs after the first 100 days. Day 100 should be considered merely a guideline, however.. The first sign of acute GVHD is usually a mild skin rash. This may change into a sunburn-like redness. In more serious cases, skin may blister or peel. Acute GVHD can also affect the gastrointestinal tract and liver. Some combination of nausea, cramping, bloody or watery diarrhea and jaundice, a yellowing of the skin and eyes, may result.. Patients who have had acute GVHD are at greatest risk for developing chronic GVHD. However, a patient who has not had acute GVHD can still have chronic GVHD, which develops three or more months after a BMT. Skin problems, including rashes, itching, changes in skin color, lesions and tautness are typical.. Other common symptoms are liver abnormalities and infections. Chronic GVHD can attack glands, ...

BACKGROUND Graft-versus-host disease (GVHD) remains a cause of long-term morbidity after allogeneic hematopoietic stem cell transplantation, and recent studies indicate that extracorporeal photophoresis (ECP) is useful for treatment of steroid-refractory GVHD although the mechanisms are unclear. Antigen-presenting cells (APCs) such as dendritic cells have a central role in GVHD, and apoptosis of APCs by HLA-DR monoclonal antibody (MoAb) has been documented in vitro and in vivo. Monocytes have been identified as precursors of dendritic cells in vivo and particularly under conditions of inflammation. STUDY DESIGN AND METHODS This study examined whether ECP altered the survival of peripheral blood monocytes from patients with GVHD, monocyte apoptosis after engagement of HLA-DR antigens with MoAb, and monocyte apoptosis after allointeraction with primary CD4+ T lymphocytes. Samples from patients from two centers were studied. RESULTS It is reported here that ECP induced apoptosis of monocytes over a

Reinisch, W., Knobler, R., Rutgeerts, P. J., Ochsenkühn, T., Anderson, F., von Tirpitz, C., Kaatz, M., van der Woude, C. J., Parenti, D. and Mannon, P. J. (2012), Extracorporeal photopheresis (ECP) in patients with steroid-dependent Crohns disease: An open-label, multicenter, prospective trial. Inflamm Bowel Dis. doi: 10.1002/ibd.23012 ...

Abstract. Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although donor T cel

Extracorporeal Photopheresis: process and mechanism. Consult best oncologists and haematologists in India. Cancer hospital in India, Apollo Hospitals.

Coadministration of ibrutinib with a strong (eg, boceprevir [Victrelis], clarithromycin, cobicistat, conivaptan [Vaprisol], posaconazole, voriconazole) or moderate (eg, aprepitant, cimetidine, ciprofloxacin, clotrimazole) CYP3A inhibitor can increase ibrutinib plasma concentrations, potentially increasing the likelihood of adverse reactions. For concomitant use with a moderate CYP3A inhibitor, the ibrutinib dose should be modified based on adverse reactions. Coadministration with posaconazole at doses higher than those specified below or other strong CYP3A inhibitors should be avoided. The ibrutinib dose should be reduced to 280 mg once daily for concurrent use with posaconazole immediate-release tablet 200 mg twice daily, posaconazole delayed-release tablet 300 mg once daily, or voriconazole at any dose. The ibrutinib dose should also be modified based on adverse reactions. If higher-dose posiconazole or other strong CYP3A inhibitors are to be used for a short period (eg, as anti-infectives for ...

Conference (2016, December 08). - Introduction: Graft-versus-host disease (GVHD) remains one of the major complications following haematopoietic stem cell transplantation (HSCT). Approximately 15% of the patients with chronic GVHD ... [more ▼]. - Introduction: Graft-versus-host disease (GVHD) remains one of the major complications following haematopoietic stem cell transplantation (HSCT). Approximately 15% of the patients with chronic GVHD develop the sclerodermatous form of the disease characterized by multiple organ fibrosis and loss of skin elasticity. Several studies have shown the potential benefits of imatinib, a tyrosine kinase inhibitor (TKI), as a treatment of fibrosis in cGVHD due to its ability to inhibit simultaneously PDGF-R and c-Abl pathways which are both involved in fibrosis mechanisms. - Aims: Some early-phase clinical studies have assessed the impact of TKIs in patients with steroid-refractory cGVHD. Unfortunately, these studies yielded to conflicting results underlying the ...

Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age ,18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, ...

Background. Acute graft versus host disease is a severe complication of allogeneic stem cell transplantation in which the functional immune cells of the donor recognize the recipient as foreign, mounting an immunological attack. The need for improved diagnostic tools for the assessment of acute graft versus host disease becomes all the more urgent in the context of a transplanted population. In the present study, a novel bioinformatics framework was used to identify gene expression patterns associated with acute graft versus host disease in patients undergoing allogenic haematopoietic stem cell transplant. Design and Method. Peripheral blood cells from acute graft versus host disease (YES) patients and from patients who did not experience acute graft versus host disease (NO) were prospectively collected. Gene expression profiling was performed using a panel of 47 candidate genes potentially involved in alloreactive responses. Collectively, the YES/NO acute graft versus host disease patient ...

Fingerprint Dive into the research topics of Selective depletion of CD8,sup,+,/sup, cells for prevention of graft-versus-host disease after bone marrow transplantation: A randomized controlled trial. Together they form a unique fingerprint. ...

Chronic Graft Versus Host Disease Webinar: Annie Im, MD and Assistant ProfessorUniversity of Pittsburgh School of Medicine. Dr. Im specializes in the long term follow up of stem cell transplant recipients and chronic graft-versus-host disease patients.

NSG mice are a proven host for engraftment of human tumors or establishment of human immunity following hematopoietic stem cell transplantation.

Ben Farhat K, Alosaimi MF, Shendi H, Al-Hammadi S, Jones J, Schwarz K, Schulz A, Alawdah LS, Burchett S, Albuhairi S, Whangbo J, Kwatra N, Shamseldin HE, Alkuraya FS, Chou J, Geha RS. Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-?B-inducing kinase deficiency. J Allergy Clin Immunol. 2019 03; 143(3):1240-1243.e4 ...

When the donor cannot be matched to a patient with bone marrow dysfunction, the donor hematopoietic stem cells may attack the host in a process called graft-versus-host disease (GVHD). DAveni et al. show that when human donors were administered granulocyte colony-stimulating factor (G-CSF) prior to collection of peripheral blood stem cells (referred to as G-CSF-mobilized stem cells), the collected cells included a previously uncharacterized population of immunosuppressive CD34+ cells that had characteristics similar to mature monocytes. In coculture experiments with these cells isolated from G-CSF-mobilized stem cells from humans or mice, the CD34+ monocytes inhibited the proliferation of activated T cells. Further experiments with the mouse CD34+ monocytes revealed that the inhibitory effect on T cells depended on interferon-γ produced by the T cells, cell-cell contact, and production of nitric oxide (NO) by the CD34+ monocytes and not only prevented proliferation but induced apoptosis of the ...

HLA-haploidentical hematopoietic stem cell transplantation is now one of the most commonly employed alternative donor techniques, with most centers applying T-c...

To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic …

Complementation analysis of a polyhydroxyalkanoate (PHA)-negative mutant of proved that ORF3 in the locus (a 402-bp gene located downstream of the PHA synthase gene) participates in PHA biosynthesis on alkanoic acids, and the ORF3 gene is here referred to as BL21(DE3) carrying under the control of the T7 promoter overexpressed enoyl coenzyme A (enoyl-CoA) hydratase, … Continue reading Complementation analysis of a polyhydroxyalkanoate (PHA)-negative mutant of proved that ORF3. ...