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Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse
Stephanie J Lee1, John P Klein, A John Barrett
1Graft vs Host Disease Working Committee of the International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI, USA. stephanie_lee@dfci.harvard.edu
Insights
Chronic graft-versus-host disease (cGVHD) impacts transplant outcomes, reducing relapse but increasing mortality. A new grading system predicts mortality, identifying low-risk patients who may avoid aggressive immunosuppression.
Area of Science:
- Hematology
- Immunology
- Transplant Science
Background:
- Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic stem cell transplantation.
- It is linked to reduced relapse rates but increased treatment-related mortality.
- Current grading systems for cGVHD are insufficient for predicting survival outcomes.
Purpose of the Study:
- To develop and validate a new grading system for cGVHD that accurately predicts survival.
- To assess the relationship between cGVHD severity and transplant outcomes, including relapse and mortality.
- To identify patients with cGVHD who may not require aggressive immunosuppression.
Main Methods:
- Developed a novel cGVHD grading system using data from 1827 HLA-matched sibling allotransplant recipients from the International Bone Marrow Transplant Registry (IBMTR).
- Identified independent prognostic variables including Karnofsky performance score, diarrhea, weight loss, and cutaneous/oral involvement.
- Validated the new system alongside existing limited/extensive and mild/moderate/severe classifications in analyses of 1092 IBMTR and 553 National Marrow Donor Program recipients.
Main Results:
- The presence of cGVHD was associated with a reduced risk of relapse (RR, 0.5-0.6) and an increased risk of treatment-related mortality (RR, 1.8-2.8).
- The newly developed grading system, along with existing classifications, could predict treatment-related mortality.
- No grading scheme correlated cGVHD severity with relapse rates.
- Patients in the most favorable cGVHD group exhibited survival and disease-free survival rates comparable to or better than those without cGVHD.
Conclusions:
- A novel grading system effectively predicts survival in cGVHD patients.
- cGVHD severity is a significant predictor of treatment-related mortality but not relapse rates.
- Patients with low-severity cGVHD may benefit from reduced or no systemic immune suppression, improving their overall outcomes.
Abstract:
Chronic graft-versus-host disease (cGVHD) is the leading cause of late treatment-related deaths among recipients of allogeneic bone marrow and blood transplants. However, cGVHD is also associated with fewer relapses. We sought to determine whether severity of cGVHD predicts the magnitude of these effects. One impediment to such an analysis is the current limited/extensive grading system for cGVHD because this classification was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of multiorgan involvement. We, therefore, first developed a grading system predictive for survival by using data from 1827 HLA-matched sibling allotransplant recipients reported to the International Bone Marrow Transplant Registry (IBMTR). We found Karnofsky performance score, diarrhea, weight loss, and cutaneous and oral involvement to be independent prognostic variables, from which we generated a grading scheme. We tested this scheme, the limited/extensive classification system, and a classification based on clinical impression of overall cGVHD severity (mild/moderate/severe) in parallel analyses of 1092 HLA-matched sibling transplant recipients from the IBMTR and 553 recipients of unrelated donor marrow from the National Marrow Donor Program. Presence of cGVHD was associated with fewer relapses (relative risk [RR], 0.5-0.6) but more treatment-related mortality (RR, 1.8-2.8) in the 3 analyses. No grading scheme correlated cGVHD severity with relapse rates, but all schemes predicted treatment-related mortality. Survival and disease-free survival of the most favorable cGVHD group in each scheme were similar, or better, than those of patients without cGVHD; these patients may not need aggressive or extended immune suppression.