Severity Stratification of Chronic Graft-Versus-Host Disease
Chronic GVHD severity is stratified into three global categories—mild, moderate, and severe—based on the number of organs involved and the degree of functional impairment in each affected organ, with this classification directly predicting mortality risk and guiding treatment intensity. 1, 2
NIH Consensus Criteria for Global Severity Assessment
The National Institutes of Health consensus criteria provide the standardized framework for severity stratification:
Mild Chronic GVHD
- Involves only 1-2 organs or sites with no clinically significant functional impairment 2
- Score of 1 in affected organs using the 0-3 organ scoring system 2
- Does not typically require systemic immunosuppressive therapy 2
Moderate Chronic GVHD
- Involves at least 1 organ or site with clinically significant functional impairment but no major disability 2
- Score of 2 in at least one affected organ, or involvement of 3 or more organs with score of 1 2
- Requires systemic corticosteroid therapy, typically 0.5-1 mg/kg/day combined with calcineurin inhibitor continuation or escalation 1, 3
Severe Chronic GVHD
- Demonstrates major disability caused by chronic GVHD manifestations 2
- Score of 3 in any affected organ indicating severe functional impairment 2
- Associated with significantly worse survival outcomes (hazard ratio 3.28 compared to mild/moderate disease) and higher non-relapse mortality (hazard ratio 3.04) 4
- Requires aggressive systemic immunosuppression, with ibrutinib as the only FDA-approved second-line therapy for steroid-refractory cases 1, 3
Organ-Specific Scoring System
Each affected organ is scored from 0-3 based on extent and functional impact:
- Score 0: No involvement 2
- Score 1: Mild involvement without significant functional impairment 2
- Score 2: Moderate involvement with clinically significant but not disabling functional impairment 2
- Score 3: Severe involvement with major functional disability 2
The organs assessed include skin, mouth, eyes, gastrointestinal tract, liver, lungs, joints/fascia, and female genital tract 2
Clinical Implications of Severity Stratification
Treatment intensity must be matched to global severity. Mild disease may be managed with topical therapies and observation, while moderate-to-severe disease requires systemic corticosteroids as first-line therapy 5. Approximately 40-50% of patients develop steroid-refractory disease, which carries high mortality risk and necessitates second-line agents 5.
Poor Prognostic Factors Within Severity Categories
- Thrombocytopenia combined with extensive disease predicts 3-year survival of only 52% even with standard prednisone plus calcineurin inhibitor therapy 6
- Progressive-type onset (evolving from acute GVHD without resolution) carries worse prognosis than de novo or quiescent onset 6
- Extensive skin involvement independently predicts poor outcomes 6
Common Pitfalls in Severity Assessment
Do not confuse the NIH classification with the older Seattle classification. The Seattle system only distinguished "limited" versus "extensive" disease based on number of organs involved, without accounting for functional impact 4. The NIH system is more accurate in predicting mortality because it reclassifies many old "extensive" cases into moderate or severe categories based on actual functional impairment 4.
Do not delay treatment while determining exact severity. Multidisciplinary care in specialized transplant centers is essential to prevent irreversible organ damage, and early recognition with prompt initiation of appropriate therapy takes priority over perfect classification 1, 3.