Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria

Area of Science:

• Pediatric Hematology and Oncology
• Stem Cell Transplantation
• Immunology

Background:

• Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are significant complications following allogeneic hematopoietic stem cell transplantation (HSCT).
• The National Institutes of Health Consensus Criteria (NIH-CC) were developed to standardize cGVHD diagnosis but lack validation in pediatric populations (<18 years).
• Accurate diagnosis and classification of GVHD syndromes in children are crucial for effective management and improved outcomes.

Purpose of the Study:

• To evaluate the applicability and reliability of the NIH-CC for diagnosing pediatric cGVHD across multiple institutions.
• To determine the incidence of cGVHD and L-aGVHD in pediatric HSCT recipients using the NIH-CC.
• To identify clinical features and risk factors associated with cGVHD and L-aGVHD in children.

Main Methods:

• A prospective, multi-institution study involving 302 pediatric patients (<18 years) undergoing HSCT.
• Patients were followed for 1 year post-transplant to monitor for cGVHD development.
• NIH-CC were applied for diagnosis, with central review and adjudication by a study committee to ensure consistency.

Main Results:

• The NIH-CC proved feasible and reliable for diagnosing pediatric cGVHD, although 28.2% of initially reported cases were reclassified, often as L-aGVHD.
• The incidence of cGVHD was 21% and L-aGVHD was 24.7%. Common sites affected were the mouth, skin, eyes, and lungs.
• Past acute GVHD, peripheral blood stem cell grafts, and recipient age ≥12 years were identified as risk factors for cGVHD and L-aGVHD. The NIH-CC for bronchiolitis obliterans syndrome showed poor performance in children.

Conclusions:

• The NIH-CC can be reliably applied to diagnose cGVHD in pediatric HSCT recipients.
• Further refinement of the NIH-CC is necessary to improve their accuracy and specificity for diagnosing GVHD syndromes in children, especially L-aGVHD and specific manifestations like bronchiolitis obliterans syndrome.
• Identifying risk factors like prior acute GVHD and graft type aids in risk stratification and potential intervention strategies for pediatric HSCT.