Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome

Area of Science:

• Pediatric Hematology/Oncology
• Transplantation Immunology
• Graft-versus-Host Disease Research

Background:

• Chronic graft-versus-host disease (cGVHD) is a significant complication post-allogeneic hematopoietic stem cell transplantation (HSCT), impacting long-term survival.
• Limited research exists on cGVHD specifically in pediatric populations, particularly concerning its antileukemic effects and impact on disease-free survival (DFS).
• Understanding cGVHD in children is crucial for optimizing HSCT outcomes and managing treatment-related toxicities.

Purpose of the Study:

• To investigate the incidence and predictive factors of cGVHD in a pediatric cohort undergoing allogeneic HSCT.
• To evaluate the impact of cGVHD on relapse rates, transplant-related mortality, and DFS in children with malignant and nonmalignant diseases.
• To explore the potential graft-versus-leukemia (GvL) effect of cGVHD, especially in acute lymphoblastic leukemia (ALL).

Main Methods:

• Retrospective analysis of 696 children who received allogeneic HSCT for malignant or nonmalignant conditions.
• Data collected included donor type, stem cell source (bone marrow, peripheral blood, cord blood), preparative regimens, and GVHD occurrence.
• Multivariate analysis was used to identify predictors of cGVHD and its association with clinical outcomes, including relapse and DFS.

Main Results:

• The cumulative incidence of cGVHD was 27% at 3 years post-HSCT, with predictors including donor/recipient age, acute GVHD severity, and use of total body irradiation.
• Cord blood (CB) transplants demonstrated a significantly lower risk of cGVHD (RR=0.07).
• In pediatric hematologic malignancies, cGVHD was associated with reduced relapse probability (16% vs. 39%) and improved DFS (68% vs. 54%), particularly in ALL patients, suggesting a GvL effect.

Conclusions:

• This study provides novel insights into cGVHD in children, highlighting the protective role of CB stem cells and non-radiotherapy preparative regimens.
• cGVHD, despite increasing transplant-related mortality, exerts a significant antileukemic effect in pediatric hematologic malignancies, notably ALL.
• The findings underscore the importance of balancing GVHD prevention with harnessing its potential GvL benefits to improve long-term DFS in pediatric HSCT recipients.