Avoidance of related donors in CAEBV with germline immune variants: long-termoutcome of matched unrelated donor HSCT - a case report

This study reports an adult-onset case of NK cell-predominant chronic active Epstein-Barr virus infection (CAEBV) harboring multiple heterozygous germline variants affecting antiviral immunity. Functional assessments of NK cell cytotoxicity and degranulation in the patient and her family members revealed subclinical immune defects in several relatives, leading to the exclusion of related donors. The patient ultimately underwent a fully HLA-matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT), achieving early virologic remission and complete donor chimerism. However, the post-transplant course was complicated by severe immune-related adverse events, including acute and chronic graft-versus-host disease (GVHD), thrombotic microangiopathy, viral reactivations, and secondary hemophagocytic lymphohistiocytosis, ultimately resulting in death due to severe pulmonary infection and multi-organ failure. This case underscores the critical role of immunogenetic risk stratification in guiding transplant decisions. Matched unrelated donor transplantation, supported by comprehensive functional and genetic screening, offers curative potential while avoiding the use of immunologically compromised donors. Nevertheless, long-term outcomes in CAEBV depend not only on virologic remission but also on sustained immune reconstitution. In addition, this report reviews precision transplantation strategies that integrate host genetic background, immune function, and viral dynamics, providing a roadmap for the future management of CAEBV.