Survivors of HCT may have more late effects, worse quality of life, and a shortened lifespan compared to people who do not undergo HCT. In people who receive stem cells from another person, unique immune mediated disorders such as chronic GVHD take a particularly high toll. Although patients may experience symptoms and organ dysfunction resembling known autoimmune syndromes or solid organ allograft rejections, the underlying biology is poorly characterized. Dr. Lee’s research program is devoted to understanding late effects and chronic GVHD, and developing better approaches to the prevention, diagnosis and treatment of these transplant-related problems.
Dr. Lee's research emphasizes survivorship challenges, quality-of-life issues, and the impact of chronic GVHD. Another area of interest is health-services research, which includes analysis of physician practices, doctor-patient communication, cost-effectiveness analysis, and similar policy issues.
In addition to her research projects, Dr. Lee is also the Research Director of the Long-Term-Follow-Up Program (LTFU) at Fred Hutch. This program follows more than 5,000 HCT survivors.
Chronic graft-versus-host disease (GVHD) is a multisystem autoimmune-like disorder occurring after allogeneic hematopoietic cell transplantation (HCT). It results in inflammation, scarring, and organ dysfunction. Chronic GVHD is the most common long-term complication of HCT, associated with an increased risk of infection (the major cause of death from chronic GVHD), potentially serious impaired organ function, and poor quality of life. Chronic GVHD affects 20% to 50% of patients.
Chronic GVHD typically involves one or more organs including skin, mouth, liver, eyes, intestinal tract, vagina, esophagus, joints, and lungs. Treatment involves taking immunosuppressive medications for several years. As a result, all patients with chronic GVHD are considered immune compromised. Any infection should be aggressively treated.
Patient may experience red rash, itching, mouth sores and sensitivity, dry eyes, diarrhea, and abnormal liver tests. More fibrotic and chronic manifestations can occur such as sclerotic and lichen-planus skin changes, fasciitis, Sjögren’s syndrome, joint contractures, esophageal strictures, and bronchiolitis obliterans.
Chronic GVHD and its therapy, specifically the prolonged exposure to immunosuppressive medications and steroids, cause significant impairment of quality of life in transplant survivors who have this complication. Quality of life and symptom surveys are often used to measure a patient’s experience of the disease.
Any post-transplant patient developing symptoms or signs suggestive of chronic GVHD should be referred for prompt evaluation. There is an unfortunate tendency to assume that all problems after an allogeneic transplant are due to chronic GVHD. It is important that new findings are systematically evaluated by a team experienced in the care of people after transplantation. An NIH conference on chronic GVHD made specific recommendations for the diagnosis of chronic GVHD including the following:
A detailed explanation of all diagnostic and distinctive signs are provided in
Histopathologic Diagnosis of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report
Toward Biomarkers for Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. Biomarker Working Group Report
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
Ancillary Therapy and Supportive Care of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group Report
The Chronic GVHD Consortium was established to conduct investigations of GVHD that occur after allogeneic stem cell transplantation. Particular emphasis is on chronic GVHD, cutaneous sclerosis, bronchiolitis obliterans syndrome, and late-acute graft-vs-host disease. Dr. Lee is the lead Principal Investigator for the consortium and holds various sub-contracts with participating sites and companies in order to conduct studies. Along with implementing various studies, the Consortium was also created to provide ongoing resource for collaboration with other investigators around the world. Below is a list of participating consortium sites as well as links to consortium research resources.