Chronic Graft-versus-Host Disease
Screening for Chronic Graft-versus-Host Disease–Associated Comorbidities
Routine periodic screening for chronic graft-versus-host disease (cGVHD)–associated comorbidities helps to ensure that the manifestations of cGVHD are responding to treatment and that modifiable risk factors are identified and treated. A systematic, or head-to-toe, approach may be useful.
Deputy Division Head
“When screening patients for cGVHD-related comorbidities, we separate the conditions that are associated with cGVHD from those that are associated with being on immunosuppressive therapy, particularly steroids.”
When screening patients for cGVHD-related comorbidities, we separate the conditions that are associated with cGVHD from those that are associated with being on immunosuppressive therapy, particularly steroids. I tell students and fellows to start at the top of the patient and work their way down for the manifestations for cGVHD. So, in other words, first we look for alopecia and eye morbidities, and then we examine the oral mucosa. We check for dry eyes, dry mouth, oral leukoplakia, and secondary oral cancer. They should have routine ophthalmologic evaluations and visits to the dentist.
Moving to the gastrointestinal tract, we look for esophageal strictures and other problems. Proper nutrition is critical for patients with cGVHD, and we need to make sure that they have adequate protein intake, their blood glucose levels are good, they have a good appetite, and they are not becoming overweight.
Then we consider the heart and lungs. Cardiovascular disease is a leading cause of late deaths in patients who have survived an allogeneic transplantation. Patients on calcineurin inhibitors and steroids tend to develop hypertension and metabolic dysregulation (eg, high cholesterol and high blood glucose), so we need to watch that and adequately control their risk factors to prevent cardiovascular events. These individuals also tend to get steroid myopathy. Thus, we should try to taper them as soon as possible and move to steroid-sparing agents as more of them become available so that we can get patients off steroids or on a lower dose. Bronchiolitis obliterans syndrome will affect a subset of patients, so longitudinal pulmonary function testing may be helpful.
Continuing down the body, the liver and kidneys require monitoring, particularly in those treated with cyclosporine or tacrolimus. Tacrolimus can affect the kidneys, and monitoring levels is essential to prevent kidney toxicities. And pancreatic insufficiency is uncommon in patients with cGVHD but may be a causative factor in those with major episodes of diarrhea. If we continue to move down, sexual health is rarely discussed with individuals with cGVHD. Female patients with cGVHD may develop vaginal strictures and dryness, while male patients may develop erectile dysfunction. These conditions should be addressed so that we can improve the lives of our patients with cGVHD. Additionally, some individuals with cGVHD develop autoimmune neuropathies and may require neurologic evaluations. I think that patients with cGVHD benefit from being monitored in a specialized clinic at least once a year.
Finally, we consider that the burden of cGVHD may put people at risk for chronic depression. These patients are not only at risk because of the steroids and/or mood disorders but also because, as transplant recipients, they have been through a major life event.
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001
Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2014 Response Criteria Working Group report. Biol Blood Marrow Transplant. 2015;21(6):984-999. doi:10.1016/j.bbmt.2015.02.025
Pavletic SZ, Martin P, Lee SJ, et al; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006;12(3):252-266. doi:10.1016/j.bbmt.2006.01.008
Sarantopoulos S, Cardones AR, Sullivan KM. How I treat refractory chronic graft-versus-host disease. Blood. 2019;133(11):1191-1200. doi:10.1182/blood-2018-04-785899
Wolff D, Herzberg PY, Herrmann A, et al. Post-transplant multimorbidity index and quality of life in patients with chronic graft-versus-host disease-results from a joint evaluation of a prospective German multicenter validation trial and a cohort from the National Institutes of Health. Bone Marrow Transplant. 2021;56(1):243-256. doi:10.1038/s41409-020-01017-8
Wood WA, Chai X, Weisdorf D, et al. Comorbidity burden in patients with chronic GVHD. Bone Marrow Transplant. 2013;48(11):1429-1436. doi:10.1038/bmt.2013.70