AimTo determine if there are correlations between joint and fascial chronic graft-vs-host disease (cGVHD) with clinical findings, laboratory parameters, and measures of functional capacity.Methods29 patients were diagnosed with cGVHD based on National Institutes of Health (NIH) Consensus Criteria at the University Hospital Centre Zagreb from October 2013 to October 2015. Physical examination, including functional measures such as 2-minute walk test and hand grip strength, as well as laboratory tests were performed. The relationship between these evaluations and the severity of joint and fascial cGVHD was tested by logistical regression analysis.Results12 of 29 patients (41.3%) had joint and fascial cGVHD diagnosed according to NIH Consensus Criteria. There was a significant positive correlation of joint and fascial cGVHD and skin cGVHD (P < 0.001), serum C3 complement level (P = 0.045), and leukocytes (P = 0.032). There was a significant negative correlation between 2-minute walk test (P = 0.016), percentage of cytotoxic T cells CD3+/CD8+ (P = 0.022), serum albumin (P = 0.047), and Karnofsky score (P < 0.001). Binary logistic regression model found that a significant predictor for joint and fascial cGVHD was cGVHD skin involvement (odds ratio, 7.79; 95 confidence interval 1.87-32.56; P = 0.005).ConclusionJoint and fascial cGVHD manifestations correlated with multiple laboratory measurements, clinical features, and cGVHD skin involvement, which was a significant predictor for joint and fascial cGVHD.
AimTo investigate the ability of two standard quality of life (QOL) questionnaires – The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria.MethodsIn this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT.ResultsThe study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P < 0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P = 0.0007) and social functioning subscale of QLQ C30 (P = 0.009).ConclusioncGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients.
Background Glycans, complex oligosaccharides, are directly involved in almost every biological process, have a fundamental role in the immune system and are probably involved in nearly every human disease. However, glycosylation has been greatly ignored in the area of allogeneic hematopoietic stem cell transplantation (alloHSCT) and graft versus host disease (GVHD). Both acute and chronic GVHD are multisystemic debilitating immunological disturbances arising after alloHSCT. Scope of Review In this paper we review the glycosylation research already done in the field of alloHSCT and GVHD, and evaluate further potential of glycan analysis in GVHD by looking into resembling inflammatory and autoimmune conditions. Major Conclusions Glycan research could bring significant improvement in alloHSCT procedure with reduction in following complications, such as GVHD. Identifying glycan patterns that induce self-tolerance and the ones that cause the auto- and allo-immune response could lead to innovative and tissue specific immunomodulative therapy instead of the current immunosuppressive treatment, enabling preservation of the graft-versus-tumor effect. Moreover, improved glycan pattern analyses could offer a more complete assessment and greatly needed dynamic biomarkers for GVHD. General Significance This review is written with a goal to encourage glycan research in the field of alloHSCT and GVHD as a perspective tool leading to improved engraftment, discovery of much needed biomarkers for GVHD, enabling an appropriate therapy and improved monitoring of therapeutic response.
Background: Chronic graft-versus-host disease (cGVHD) is a disorder that affects many organ systems in highly variable fashion occurring in approximately 50% of patients following allogeneic hematopoietic stem cell transplantation (alloHSCT). It is the major cause of non-relapse morbidity and mortality after alloHSCT in individuals otherwise cured of their hematologic diseases, inducing poor quality of life, impaired functional status, inability to work, and need for ongoing chronic care, which has also important impact to health-related costs. cGVHD Consensus Conference held in 2005 at the National Institutes of Health (NIH), USA, produced recommendations regarding cGVHD diagnosis, staging, histopathology, response criteria, biomarkers, ancillary and supportive care, and design of clinical trials. In 2014, second cGVHD NIH Consensus Conference updated these recommendations, published during 2015 as 6 papers in Biology of Blood and Marrow Transplantation (BBMT) journal. Although practitioners are generally familiar with the NIH recommendations, many barriers prevent their greater uptake in clinical practice. In order to overcome these challenges, in 2013 multidisciplinary clinic infrastructure was organized at the University Hospital Center (UHC) Zagreb, Croatia, in collaboration with the NIH leading scientists, using established cGVHD-related grading scales and measurements. Methods: Division of Hematology, UHC Zagreb, Croatia, has experience with alloHSCT since 1983, and 827 patients received alloHSCT until the end of 2014. Since the establishment of multidisciplinary cGVHD team in 2013, patients were enrolled into the Unity through Knowledge Fund (UKF) study protocol (funded by World Bank and Croatian Ministry of Science, Education and Sports) and examined by multiple subspecialists, firstly seen by hematologist, with detailed history and physical exam. Standard cGVHD scoring forms are filled according to NIH Consensus recommendations, and extensive laboratory analyses were done. Patients are seen and evaluated by other sub-specialists (Dental, Dermatology, Rehabilitation, Neurology, Ophthalmology, Gynecology, and other) with further workup as needed. Quality of life questionnaires are filled during the visit. All data are collected in a specially developed database and weekly team meetings were established. Blood and small biopsy tissue samples (skin, mouth) are stored for further research. Results: Using multidisciplinary approach since 2013, 46 (6 pediatric) cGVHD patients were assesed, median age was 41 years; range [9-71], 24 were male and 22 were female. The median time from transplant to enrollment was 20 months [2-258], from cGVHD diagnosis to enrollment 7 months [0.03-234] and from transplant to cGVHD diagnosis 10 months [2-128]. Additional 17 post-alloHSCT patients were eveluated, but without confirmation of cGVHD diagnosis. Among cGVHD patients, 31 (67%) of them received transplants from matched related donors, 27 (59%) of them had myeloablative conditioning, and 26 (57%) received peripheral blood stem cells as graft source. Thirty-five (76%) patients had previous acute GVHD, 11 (24%) had de novo cGVHD, 21 (46%) quiescent and 14 (30%) progressive onset; 41 (89%) were classified as classic and 5 (11%) as overlap; 23 (50%) patients had severe, 19 (41%) moderate, and 4 (9%) mild global cGVHD score. The most involved organs were skin (54%), eyes (50%), lungs (48%) and mouth (39%). Due to internationally peer reviewed UKF grant awarded in 2013 doctoral and postdoctoral researcher were hired, and visits of young clinicians to NIH and other cGVHD centers were realized. Several new research subprojects emerged since formation of our cGVHD team and applications to the new project calls were submitted. Also, 2 international cGVHD symposiums were organized in Zagreb, Croatia, in last 2 years stimulating education and networking. Conclusion: Implementation of NIH criteria for standardizationof cGVHD in Croatia showed remarkable results, not just improving quality of medical documentation and management of these long-terms survivors with complex and long-lasting health issues, but also facilitating further international clinical research and collaboration with cGVHD community, with potential positive impact to health-related costs and benefit to society. Disclosures Nemet: Pliva: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria.
Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and a major late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). The disease is characterized by an altered homeostasis of the humoral immune response. Immunoglobulin G (IgG) glycoprotein is the main effector molecule of the humoral immune response. Changes in IgG glycosylation are associated with a number of autoimmune diseases. IgG glycosylation analysis was done by the means of liquid chromatography in the National Institutes of Health (NIH) cohort of 213 cGvHD patients. The results showed statistically significant differences with regards to cGvHD NIH joint/fascia and skin score, disease activity and intensity of systemic immunosuppression. ROC analysis confirmed that IgG glycosylation increases specificity and sensitivity of models using laboratory parameters and markers of inflammation associated with cGvHD (eosinophil count, complement components C3 and C4 and inflammation markers: albumin, CRP and thrombocyte count). This research shows that IgG glycosylation may play a significant role in cGvHD pathology. Further research could contribute to the understanding of the disease biology and lead to the clinical biomarker development to allow personalized approaches to chronic GvHD therapy.
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