AUTHOR=Wang Wenwen , Chen Jianlin , Guan Lingsu TITLE=Case Report: dose adjustment of orelabrutinib for managing central nervous system post-transplant lymphoproliferative disorder following acute lymphoblastic leukemia transplantation JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1597119 DOI=10.3389/fimmu.2025.1597119 ISSN=1664-3224 ABSTRACT=We report a case of acute B-cell leukemia complicated by central nervous system (CNS) post-transplant lymphoproliferative disorder (PTLD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patient achieved sustained disease stabilization following therapeutic dose modification of orelabrutinib, representing the first evidence-based documentation that Bruton’s tyrosine kinase (BTK) inhibitor down-titration confers clinical efficacy in PTLD. Epstein-Barr virus (EBV)-associated PTLD is a serious complication following allogeneic HSCT, with frequent CNS involvement. Effective treatment for CNS involvement is often hampered by the challenge of drug penetration across the blood-brain barrier. This case highlights the potential benefit and safety of dose-adjusted orelabrutinib in controlling CNS PTLD, suggesting a promising therapeutic approach.