Chronic graft-versus-host disease (cGVHD) is a complex complication following allogeneic stem cell transplantation. This condition arises when immune cells from a donor perceive the recipient’s healthy tissues as foreign and launch an attack against them. A structured grading system is essential for assessing and managing cGVHD, providing a framework to understand its severity and guide interventions.
Chronic Graft-Versus-Host Disease Explained
Chronic graft-versus-host disease develops when immune cells, specifically T cells, from a transplanted donor’s bone marrow or peripheral blood stem cells identify the recipient’s healthy cells as a threat. This immune response leads to inflammation and damage in various organs and tissues throughout the body. It is a significant concern for individuals who have undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT), a procedure used to treat certain cancers and blood disorders.
It is distinct from acute GVHD, which typically manifests within the first 100 days post-transplant and primarily affects the skin, liver, and gastrointestinal tract. In contrast, cGVHD generally appears later, often after 100 days, though it can emerge months or even years following transplantation. The clinical features of cGVHD are also broader, potentially impacting nearly any organ, including the skin, mouth, eyes, lungs, joints, fascia, and genital tract, presenting a wider array of symptoms compared to its acute counterpart.
Why Grading is Essential
Grading chronic GVHD serves several purposes in patient care and research. It provides a standardized method for medical professionals to assess the disease’s extent and impact, ensuring consistent evaluation and clear communication among multidisciplinary teams.
It helps guide initial treatment decisions, allowing clinicians to tailor therapies based on disease severity. It also helps predict a patient’s long-term outlook, as higher grades often correlate with more extensive disease and a less favorable prognosis. Grading systems are also used in clinical trials, enabling researchers to objectively measure treatment responses and develop new therapies for cGVHD.
Methods of Grading Chronic GVHD
The National Institutes of Health (NIH) Consensus Criteria is the most widely recognized method for grading chronic GVHD, refined over time with a significant revision in 2014. This system involves assessing multiple organ systems affected by the disease. Eight specific organs are evaluated: the skin, mouth, eyes, liver, lungs, gastrointestinal tract, joints and fascia, and the genital tract.
Each organ is assigned a severity score from 0 to 3, where 0 indicates no involvement and 3 signifies severe functional impairment. For example, skin involvement is scored based on the percentage of body surface area affected and the presence of features like sclerosis (skin tightening). Lung involvement considers aspects like forced expiratory volume in one second (FEV1). The mouth and eyes are assessed for symptoms like dryness and impact on daily activities.
These organ scores contribute to an overall global severity score, categorizing the disease as mild, moderate, or severe. Mild disease is characterized by involvement of two or fewer organs, with no more than a score of 1 in any organ and no lung involvement. Moderate disease might involve three or more organs with a score of 1, or any organ with a score of 2, or lung involvement with a score of 1. Severe disease is indicated by any organ having a score of 3, or lung involvement with a score of 2. This organ-specific scoring and global categorization provides a comprehensive picture of the disease’s impact.
Interpreting Grading Results
The overall grade assigned to chronic GVHD—mild, moderate, or severe—directly influences treatment strategies and patient monitoring. A mild grade suggests the disease is limited, potentially affecting one or two organs with minimal impact on daily life. Patients with mild cGVHD might be managed with topical or local therapies, such as skin creams or eye drops, to address specific symptoms without requiring widespread immune suppression.
For moderate cGVHD, the disease is typically more extensive, involving more organs or presenting with more significant symptoms. This level of severity usually necessitates systemic immunosuppressive treatment to control the immune response. Severe cGVHD indicates widespread and significant organ involvement, often with substantial functional impairment. Patients with severe disease generally require more aggressive and prolonged systemic therapies to manage the condition and prevent further damage. The grade also helps anticipate the long-term prognosis, with higher grades generally associated with a greater risk of complications and mortality, often due to infections from prolonged immune suppression.