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
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 ...
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)
1. IntroductionThe curative efficiency of allogeneic hematopoietic cell transplantation (HCT) is considerably dampened by the graft-versus-host disease (GVHD) that leads to significant mortality and morbidity. Donor T cells subsets are recognized as the main cellular mediators and effectors of acute GVHD (aGVHD). T cell interactions with antigen-presenting cells (APC) of both host and donor origin are required to achieve the status of
Restoration of chronic graft vs host disease (Cgvhd)-induced autoantibody (autoAb) by human granulocyte-colony stimulation factor (huG-CSF) correlates with CD4+
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 ...
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.
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Following allogenic hematopoietic stem cell transplantation (HSCT), patients with autoimmune disease or hematopoietic malignancy may develop acute or chronic graft-versus-host (GvH) disease. B lymphocytes, from the recipient as well as from the donor, have recently been implicated in the pathogenesis of such disturbances. Their deleterious effects are accounted for by other tasks B lymphocytes accomplish than the antibody production. We highlight herein some recent observations in the context of B cells in the GvH disease.
High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. Ponce DM, Hilden P, Mumaw C, Devlin SM, Lubin M, Giralt S, Goldberg JD, Hanash A, Hsu K, Jenq R, Perales MA, Sauter C, van den Brink MR, Young JW, Brentjens R, Kernan NA, Prockop S, OReilly RJ, Scaradavou A, Paczesny S, Barker JN. Blood. 2015 Jan 1;125(1):199-205.. Various forms of tissue damage and danger signals following hematopoietic stem-cell transplantation. Ramadan A, Paczesny S. Front Immunol. 2015 Jan 28;6:14.. ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease. Zhang J, Ramadan A, Griesenauer B, Li W, Turner M, Liu C, Kapur R., Hanenberg H., Blazar BR, Tawara I, and Paczesny S. Sci Transl Med 2015, 7(308): 308ra160 ...
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The purpose of this study is to validate the diagnostic and prognostic utility of our tissue-based assay, the aim is to perform a multi-institution, retrospective study of our assay compared with the current clinical gold standard (clinicopathologic correlation and prospective observation of clinical course, respectively). ...
TY - JOUR. T1 - CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. AU - Laing, S. T.. AU - Griffey, Stephen M. AU - Moreno, M. E.. AU - Stoddart, C. A.. PY - 2015. Y1 - 2015. N2 - Immunocompromised mice that can support a human immune system are an increasingly important model for the investigation of haemopoietic stem/progenitor cell (HSPC) development and human infectious disease. NOD-SCID IL-2Rgγ-/- (NSG) mice engrafted with human fetal liver and thymus prior to HSPC engraftment, commonly known as NSGebone marrow-liver-thymus (NSG-hu-BLT) mice, are one such model and have robust reconstitution of human leucocytes within the peripheral blood and tissues. Four NSG-hu-BLT mice were submitted for diagnostic necropsy examination following the development of alopecia, pruritus and lethargy after HSPC engraftment. Histopathology revealed multifocal to coalescing single keratinocyte cell death in the epidermis and follicles with dermatitis and ...
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Although many factors are known to influence hematopoietic cell transplant (HCT)2 outcomes, including the age of the recipient, comorbidity, conditioning intensity, donor source, donor-recipient human leukocyte antigen (HLA) compatibility, conditioning regimen, and posttransplant graft-versus-host disease (GVHD) prophylaxis, they incompletely predict results. Biomarkers promise to further refine our ability to risk-stratify individual patients for the likelihood of a certain events occurrence. It is important to define the clinical context of the use of biomarker(s) of interest and the outcome data that will be captured to assess a clinical endpoint, for example, grade II acute GVHD (aGVHD) or 6-month nonrelapse mortality (6m-NRM). Once the biomarkers are validated, risk stratification may allow prevention of complications via a biomarker-based personalized treatment approach. To develop the best biomarkers, the 2014 NIH Chronic GVHD Consensus Biomarker Working Group, which included world ...
Two papers published this week investigate how graft versus host disease might be predicted after hematopoietic cell transplantation.
Graft‐versus‐host disease (GVHD) represents a special situation in transplantation immunology in which immunocompetent donor cells are engrafted into recipients that are incapable of rejecting them due to tolerance, immaturity, or radiation‐ or chemotherapy‐induced immune deficiency
A simple questionnaire that rates breathing difficulties on a scale of 0 to 3 predicts survival in chronic graft-vs.-host disease (GVHD), according to a current study.
Kuang P, Dong T, Wang L, Wei X, Liu T. Tacrolimus versus cyclosporine A for prevention of graft versus host disease after stem cell transplantation. Cochrane Database of Systematic Reviews 2016, Issue 5. Art. No.: CD009208. DOI: 10.1002/14651858.CD009208. ...
The primacy of the gastrointestinal (GI) tract in dictating the outcome of graft-versus-host disease (GVHD) is broadly accepted; nevertheless, the mechanisms managing this effect are understood poorly. on donor Testosterone levels cells, leading to their emigration into the GI system where they mediate fulminant disease. These data recognize a vital, distinct anatomically, donor DC subset that amplifies GVHD. We showcase multiple healing goals and the capability of GVHD hence, once started by receiver antigen-presenting cells, to generate a unique, localised, and lethal feed-forward cascade of donor DCCmediated indirect alloantigen cytokine and GBR-12909 display release within the GI system. Allogeneic hematopoietic control cell transplantation is certainly a therapy for hematopoietic malignancies in which treat is certainly attained by immune-mediated graft-versus-leukemia (GVL) results. Graft-versus-host disease (GVHD) is certainly a equivalent procedure whereby regular tissues, especially ...
Whangbo JS, Kim HT, Mirkovic N, Leonard L, Poryanda S, Silverstein S, Kim S, Reynolds CG, Rai SC, Verrill K, Lee MA, Margossian S, Duncan C, Lehmann L, Huang J, Nikiforow S, Alyea EP, Armand P, Cutler CS, Ho VT, Blazar BR, Antin JH, Soiffer RJ, Ritz J, Koreth J. Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children. Blood Adv. 2019 09 10; 3(17):2550-2561 ...