204 research outputs found
Glycoprotein YKL-40: a novel biomarker of chronic graftvs- host disease activity and severity?
Aim To investigate whether increased YKL-40 levels positively
correlate with graft-vs-host disease (cGVHD) activity
and severity and if YKL-40 could serve as a disease biomarker.
Methods This case-control study was conducted at the
University Hospital Centre Zagreb from July 2013 to October
2015. 56 patients treated with hematopoietic stem
cell transplantation (HSCT) were included: 35 patients with
cGVHD and 21 without cGVHD. There was no difference
between groups in age, sex, median time from transplant
to study enrollment, intensity of conditioning, type of donor,
or source of stem cells. Blood samples were collected
at study enrollment and YKL-40 levels were measured with
ELISA. Disease activity was estimated using Clinician’s Impression
of Activity and Intensity of Immunosuppression
scales and disease severity using Global National Institutes
of Health (NIH) score.
Results YKL-40 levels were significantly higher in cGVHD
patients than in controls (P = 0.003). The difference remained
significant when patients with myelofibrosis were
excluded from the analysis (P = 0.017). YKL-40 level significantly
positively correlated with disease severity (P < 0.001;
correlation coefficient 0.455), and activity estimated using
Clinician’s Impression of Activity (P = 0.016; correlation coefficient
0.412) but not using Intensity of Immunosuppression
(P = 0.085; correlation coefficient 0.296).
Conclusion YKL-40 could be considered a biomarker of
cGVHD severity and activity. However, validation in a larger
group of patients is warranted, as well as longitudinal
testing of YKL-40 levels in patients at risk of developing
cGVHD
Which questionnaires should we use to evaluate quality of life in patients with chronic graft-vs-host disease?
Aim To 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.
Methods In 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.
Results The 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).
Conclusion cGVHD 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
Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: A Chronic Graft-versus-Host Disease Consortium study
Background The National Institutes of Health Consensus Conference proposed the term “overlap” graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present. Design and Methods We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to “classic” chronic graft-versus-host disease without any acute features. Results Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P\u3c0.001), and had a lower platelet count at onset of the graft-versus-host disease (P\u3c0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1–4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2–8.3; P=0.02) than classic chronic graft-versus-host disease. Conclusions These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: III. The 2014 Biomarker Working Group Report
Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic GVHD after allogeneic hematopoietic cell transplantation (HCT) or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include: a) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity, b) prognostic risk to develop chronic GVHD, and c) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well-documented following established quality control guidelines for sample acquisition, processing, preservation and testing, at intervals that are both calendar- and event-driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for utilization in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a four-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines
The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows:
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Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps.
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Develop working hypotheses/overriding concepts for chronic GVHD development.
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Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies.
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Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations.
This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD
National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee
The National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Each of the Workshop’s 6 Working Committees has published individual reports of ongoing basic, translational, and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention, and treatment. This document summarizes each committee’s recommendations and suggests 3 major initiatives for a coordinated research effort to address the problem of relapse after allo-HSCT: (1) to establish multicenter correlative and clinical trial networks for basic/translational, epidemiologic, and clinical research; (2) to establish a network of biorepositories for the collection of samples before and after allo-HSCT to aid in laboratory and clinical studies; and (3) to further refine, implement, and study the Workshop-proposed definitions for disease-specific response and relapse and recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplantation organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse after allo-HSCT
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