Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium.
ABSTRACT Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT.
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ABSTRACT: GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints orgastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.Bone Marrow Transplantation advance online publication, 31 March 2014; doi:10.1038/bmt.2014.59.Bone marrow transplantation 03/2014; · 3.00 Impact Factor
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ABSTRACT: Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.Bone Marrow Transplantation advance online publication, 17 February 2014; doi:10.1038/bmt.2014.15.Bone marrow transplantation 02/2014; · 3.00 Impact Factor
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ABSTRACT: Using the National Institutes of Health (NIH) consensus document on criteria for chronic Graft-versus-Host Disease (cGvHD), we assessed the prevalence, symptoms and clinical features of female genital chronic Graft-versus-Host Disease (cGvHD) in a cross-sectional population-based study. Forty-two women were seen at 13-148 (median 80) months after HCT. Medical history, ongoing medication, and genital symptoms and signs were registered. Gynecological examination for the diagnosis and clinical scoring of genital cGvHD was combined with clinical scoring of extra-genital cGvHD for the estimation of each individual´s global cGvHD score. Biopsies from genital mucosa were obtained from 38 patients. Genital cGvHD was diagnosed in 22/42 (52%) patients, and compared to women without genital cGvHD its presence was associated with systemic corticoid steroid treatment of extra-genital cGvHD (p=0.001), older age (p=0.07), and HCT from a sibling donor (p=0.002). Five patients had isolated genital cGvHD. Dryness, pain, smarting pain (p<0.05 for all) and dyspareunia (p=0.001) were observed more frequently (p<0.05 for all) in the group of women with genital cGvHD. Twelve patients had advanced genital cGvHD (clinical score 3) which was the main factor explaining the high rate (15/42) of severe global cGvHD. The rate of genital cGvHD was similar (p=0.37) in patients with a follow-up of ≥80 months (10/22) or <80 months (12/20). We found no convincing relationship between clinical diagnosis and histopathological assessment of mucosal biopsies. In our group of women with a long follow-up after HCT, genital cGvHD was common and in many cases not correctly diagnosed. Genital cGvHD was found to cause genital symptoms and affect sexual life and may present without any other cGvHD. Thus, there is a need for early and continuous gynecological surveillance in all women after HCT.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2014; · 3.15 Impact Factor