National Institutes of Health (NIH) Chronic GVHD Staging in Severely Affected Patients: Organ and Global Scoring Correlate with Established Indicators of Disease Severity and Prognosis.
ABSTRACT Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute (NCI) cross-sectional chronic Graft-versus-Host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures including the 2005 NIH Consensus Project cGVHD severity score. The purpose of this study is to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in order to standardize clinician evaluation and staging of cGVHD. 125 of 189 patients met criteria for severe cGVHD on the NIH global score and 62 had moderate disease, with a median of 4 (range 1-8) involved organs. Clinician average NIH organ score and the corresponding organ scores performed by subspecialists were highly correlated (r=0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures including Lee Scale, SF-36 Physical Component Scale (PCS), 2 minutes walk, grip strength, range of motion and Human Activity Profile (HAP). Joints/fascia, skin, and lung involvement impacted function and quality of life most significantly and showed highest number of correlations with outcome measures. The final Cox model showing factors jointly predictive for survival contained the time from cGVHD diagnosis (>49 vs. ≤49 months, HR=0.23; p=0.0011), absolute eosinophil count of (0-0.5 vs. >0.5 cells/μL, HR=3.95; p=0.0006) at the time of NIH evaluation, and NIH lung score (3 vs. 0-2, HR= 11.02; p <0.0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. Strong association with subspecialist evaluation suggests that NIH organs and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex sub-specialist exams. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors.
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ABSTRACT: B cells are implicated in the pathophysiology of chronic GVHD and phase II trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that post-transplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65 patient phase II trial of rituximab (375 mg/m(2) iv), administered at 3, 6, 9 and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31% respectively, both lower than the corresponding rates in a concurrent control cohort (60%, p=0.1 and 48.5%, p=0.015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs. 19%, p=0.02) and overall survival was superior at 4 years (71% vs. 56%, p=0.05). At 2 years from transplantation, the BAFF/B cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (p=0.039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial. Trial registered at www.clinicaltrials.gov (NCT00379587).Blood 07/2013; 122(8). DOI:10.1182/blood-2013-04-495895 · 10.43 Impact Factor
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ABSTRACT: In 2005, the National Institutes of Health (NIH) consensus conference published a series of papers recommending methods to improve the conduct of clinical trials in chronic GVHD. Although the NIH recommendations were primarily aimed at strengthening research, several papers addressed issues relevant for clinical practice, particularly diagnosis, severity scoring, and ancillary and supportive care practices. We conducted an international survey to assess the uptake of these recommendations, identify barriers to greater use and document the use and perceived effectiveness of available treatments. The response rate for the American survey of 1387 practitioners was 21.8%, and it was 24.6% for 407 centers surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar with the NIH consensus recommendations (94-96%) and used them in practice. Multiple barriers to greater use were reported. Besides lack of time (55-62%), unfamiliarity with the recommendations, scarcity of evidence supporting the impact of recommendations on outcomes, insufficient training/experience in chronic GVHD management and inaccessibility of subspecialists were also endorsed. Systemic corticosteroids were reported to be the most effective treatment for chronic GVHD, but many others were perceived to have moderate or great success. Therapeutic management of steroid-refractory chronic GVHD was identified as the highest priority for research.Bone Marrow Transplantation advance online publication, 19 August 2013;. doi:10.1038/bmt.2013.129.Bone marrow transplantation 08/2013; 49(1). DOI:10.1038/bmt.2013.129 · 3.47 Impact Factor
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ABSTRACT: The number of survivors following allogeneic hematopoietic stem cell transplantation (HSCT) continues to increase, yet their survivorship experience has not been fully characterized. This study examines the health status and health-related quality of life (HRQL) of HSCT survivors. The aims of the study were to: 1) explore the baseline and change over time in these health outcomes, and 2) characterize subgroups experiencing adverse outcomes. In this longitudinal study, adults who survived >3 years from date of allogeneic HSCT completed a series of patient-reported outcome measures annually, including measures of health status, HRQL and symptoms. Data were analyzed using hierarchical linear modeling. Subjects (N=171) were on average 44 (+13.5) years of age, and primarily male (62.6%); 40% were Hispanic. Mean scores for physical and mental health, and HRQL were preserved relative to population norms. Hierarchical linear modeling (HLM) revealed no significant change in the mean trajectories of these outcomes, although significant between-individual variability was observed. When controlling for demographic and clinical factors, physical symptom distress negatively affected all outcomes. The impact of symptom distress on physical health varied based on time since HSCT; impairment in physical health was greatest in survivors experiencing high symptom distress and who were within the first decade post-transplant. Extended treatment with systemic immunosuppressive therapy also predicted inferior physical health. These findings suggest that patient-centered outcomes are preserved relative to normative values and generally stable following allogeneic HSCT, although survivors with persistent symptomsand those receiving systemic immunosuppression experience impairments in health status and HRQL.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2013; 20(3). DOI:10.1016/j.bbmt.2013.12.001 · 3.35 Impact Factor