CURRENT PERSPECTIVES ON THE MANAGEMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE IN PEDIATRIC TRANSPLANTATION

Background: Hematopoietic stem cell transplantation (HSCT) has expanded its scope as a curative therapy for a wide range of severe pediatric diseases. However, its efficacy is frequently challenged by graft-versus-host disease (GVHD), a significant and potentially fatal complication. This is particularly relevant in the pediatric population, where unique immunological and physiological factors contribute to a distinct disease course. Objective: This narrative review synthesizes the current evidence base on the treatment and management of GVHD in pediatric patients. It aims to provide a critical appraisal of the unique immunological determinants, current prophylactic and treatment interventions, and the long-term morbidities and clinical needs for this specific field. Methods: A comprehensive systematic search of databases, including PubMed, Embase, and the Cochrane Library, was conducted to identify relevant literature. Articles were selected based on inclusion criteria focusing on GVHD management in patients aged 18 or younger, while excluding non-peer-reviewed articles and case reports. Data on study design, patient populations, treatment regimens, and key outcomes were extracted and synthesized. Summary: The pathogenesis of acute GVHD (aGVHD) is described by the classic three-phase model, beginning with host tissue damage, followed by donor T-cell activation, and culminating in targeted organ destruction, particularly in the skin, liver, and gastrointestinal tract. Diagnostic methods have evolved from clinical and histological assessments to include advanced biomarker-driven approaches, such as the MAGIC algorithm, which provides more precise prognostic risk stratification. Current prophylaxis strategies primarily involve calcineurin inhibitors in combination with methotrexate or mycophenolate mofetil. Novel agents like ruxolitinib and vedolizumab are emerging as promising therapeutic tools for both prophylaxis and the treatment of steroid-refractory disease. Despite these advancements, significant clinical gaps persist, as many established guidelines for GVHD management are not tailored to the pediatric population. The evident age-related disparity in GVHD risk highlights the critical need for pediatric-specific research. Conclusion: While substantial progress has been made in understanding and treating GVHD, there is a clear and urgent need for further research focused on pediatric-specific protocols. Continued efforts to validate existing therapies in pediatric cohorts, explore novel agents, and leverage biomarkers are essential to improve outcomes and the quality of life for young patients undergoing HSCT.