Treatment-related neuroanatomical and functional consequences of hematopoietic stem cell transplantation: A comprehensive review of brain structure and function

Abstract Hematopoietic stem cell transplantation (HSCT) is a foundational treatment for hematological disorders. While its efficacy is established, the conditioning regimens required for HSCT (high-dose chemotherapy and radiotherapy), along with transplant-related immunological and metabolic changes, can induce significant neurological complications. These treatment-related effects necessitate a comprehensive evaluation of their impact on brain structure and function. A synthesis of current evidence on these neurological outcomes is essential to guide clinical practice and future research. This review synthesizes literature on the effects of HSCT-associated treatments on neuroanatomy, cognitive performance, and long-term neurological sequelae. Evidence indicates consistent reductions in gray-matter volume, particularly within frontal, temporal, and parietal cortices, alongside diffuse white-matter alterations affecting major commissural and association tracts. These structural changes correlate with clinically meaningful deficits in attention, executive function, and memory. The underlying pathogenic mechanisms are multifactorial, involving direct neurotoxicity from conditioning regimens, systemic and neuroinflammatory responses, and oxidative stress. The findings underscore the importance of integrating thorough neurological evaluation and longitudinal monitoring into routine care for HSCT recipients. Future research should elucidate detailed mechanisms and develop personalized, evidence-based neuroprotective and rehabilitative strategies. A deeper understanding of these neurological consequences is paramount for improving outcomes and long-term quality of life.