Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis.

Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments.

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease.

The National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients, and the guidelines are based on experience with other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD because of prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤-2.5) at 3 anatomic sites-the femoral neck (FN), lumbar spine (LS), and total hip (TH)-and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN, P < .0001; LS, P = .0002; TH, P < .0001), malnutrition (FN, P = .0002; LS, P = .03; TH, P = .0076), higher platelet count (FN, P = .0065; TH, P = .0025), higher average National Institutes of Health organ score (FN, P = .038), higher prednisone dose (LS, P = .032), lower complement component 3 (LS, P = .0073), and physical inactivity (FN, P = .01) were associated with osteoporosis in at least 1 site. T-scores were significantly lower in the FN compared with the LS or TH (P < .0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in patients with cGVHD and osteoporosis has not been reported previously and represents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation.

Rates and Predictors of Nonadherence to the Post-Allogeneic Hematopoietic Cell Transplantation Medical Regimen in Patients and Caregivers.

Allogeneic hematopoietic cell transplantation (HCT) requires a complex, multicomponent medical regimen after hospital discharge. Patients must manage multiple medications; care for their catheter; minimize exposure to sources of potential infection; follow diet, exercise, and self-care guidelines; and attend frequent follow-up medical appointments. Their caregivers are tasked with helping them manage the regimen. Despite the importance of this management in preventing adverse clinical outcomes, there has been little study of regimen nonadherence and its predictors. We sought to prospectively determine rates and predictors of nonadherence to components of the post-HCT medical regimen during the first 8 weeks after hospital discharge. Patients (n = 92) and their caregivers (n = 91) (total n = 183) completed interview assessments pre-HCT, and at 4 weeks and 8 weeks after hospital discharge post-HCT. Sociodemographic factors (eg, age, sex), patient clinical status (eg, disease type, donor type), patient and caregiver self-reported health-related factors (eg, medical comorbidities), and patient and caregiver psychosocial factors (eg, anxiety, depression, HCT task-specific and general self-efficacy, relationship quality) were assessed pre-HCT. Nonadherence to each of 17 regimen tasks was assessed at 4 and 8 weeks after hospital discharge via self and caregiver collateral reports. Nonadherence rates varied among tasks, with 11.2% to 15.7% of the sample reporting nonadherence to immunosuppressant medication, 34.8% to 38.6% to other types of medications, 14.6% to 67.4% to required infection precautions, and 27.0% to 68.5% to lifestyle-related behaviors (eg, diet/exercise). Nonadherence rates were generally stable but worsened over time for lifestyle-related behaviors. The most consistent nonadherence predictors were patient and caregiver pre-HCT perceptions of lower HCT task efficacy. Higher caregiver depression, caregiver perceptions of poorer relationship with the patient, having a nonspousal caregiver, and having diseases other than acute myelogenous leukemia also predicted greater nonadherence in 1 or more areas. Rates of nonadherence varied across tasks, and both patient and caregiver factors, particularly self-efficacy, predicted nonadherence. The findings highlight the importance of considering not only patient factors, but also caregiver factors, in post-HCT regimen nonadherence.