Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for a variety of pediatric hematologic and non-malignant disorders, yet chronic graft-versus-host disease (cGVHD) remains the primary cause of long-term non-relapse morbidity and mortality. The incidence of cGVHD in children has been increasing, a trend associated with the expanded use of peripheral blood stem cells and unrelated donors. Despite generally lower rates than adults, cGVHD remains a significant and growing clinical problem with profound long-term implications for pediatric survivors, who have a much greater life expectancy. Objective: This review aims to provide a focused and much-needed overview of cGVHD in children. Specifically, it delineates the unique epidemiological, pathobiological, and clinical characteristics that distinguish the disease in this population, including immunological distinctions, diagnostic challenges, and special considerations for long-term effects. This report highlights the pressing questions in treatment and research, addressing the historical lack of specialized data and emphasizing the principle that "children are not small adults" in the context of this complex condition. Methods: This review was conducted by systematically analyzing and synthesizing peer-reviewed articles, clinical guidelines, and consensus statements related to pediatric cGVHD. A comprehensive literature search was performed across databases including PubMed, Scopus, and Embase using a combination of keywords such as "pediatric," "chronic GvHD," "children," "hematopoietic stem cell transplantation," "management," "diagnosis," and "long-term effects." Summary: The lower incidence and severity of cGVHD in children are attributable to distinct biological factors, including superior thymic function and a greater use of bone marrow or cord blood grafts. However, diagnostic challenges persist due to non-specific symptoms and the limitations of adult-derived criteria. The profound and age-specific impacts of the disease and its treatments on growth, neurocognitive development, and infectious risk underscore the disproportionate long-term burden on pediatric survivors. The review discusses therapeutic strategies that prioritize steroid-sparing regimens and the integration of novel targeted inhibitors and cellular therapies. Conclusion: A paradigm shift is necessary, advocating for dedicated pediatric research, age-adapted diagnostic tools, and a multidisciplinary, holistic approach to long-term survivorship care to optimize the functional status and quality of life for children with cGVHD.
Kmieć et al. (Wed,) studied this question.