Fluid Overload Syndrome is Associated With Increased Non-Relapse Mortality After Allogeneic Hematopoietic Stem Cell...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains associated with substantial non-relapse mortality (NRM) despite advances in supportive care. Fluid overload syndrome is a frequent but underrecognized complication during conditioning and the early post-transplant period. Although fluid overload is known to worsen outcomes in critical illness and heart failure, its prognostic impact in allo-HSCT has not been systematically evaluated. The aim of this analysis was to systematically assess the association between fluid overload syndrome and survival outcomes following allogeneic hematopoietic stem cell transplantation. We conducted a systematic review in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD42025634151). PubMed, Cochrane Register, ClinicalTrials.gov, and additional sources were searched for studies reporting fluid overload syndrome and survival outcomes after allo-HSCT. Study quality was assessed using the Newcastle-Ottawa Scale. Due to heterogeneity in definitions of fluid overload syndrome and in outcome reporting, a narrative synthesis was performed. We performed exploratory quantitative aggregation using Fisher's combined P-value method. Nine retrospective single-center studies comprising 2410 patients met inclusion criteria. Definitions and grading systems for fluid overload syndrome varied substantially, with reported incidences ranging from 4% to 37%. Eight of nine studies demonstrated significantly reduced overall survival (OS) in patients who developed fluid overload syndrome. Five of six studies reported significantly increased NRM, with the remaining study showing a non-significant adverse trend. Fisher's method demonstrated highly significant aggregated effects for OS (χ² = 96.9, P < .0001) and NRM (χ² = 66.43, P < .0001). Fluid overload syndrome is consistently associated with inferior overall survival and increased non-relapse mortality after allo-HSCT. Despite heterogeneity in definitions, the direction of effect is remarkably uniform across studies. Given that fluid administration is a modifiable component of supportive care, these findings support the integration of fluid stewardship strategies into transplant management. Standardized definitions, prospective multicenter studies, and mechanistic investigations are urgently needed to refine risk stratification and improve outcomes in allo-HSCT recipients.