Poor graft function after allogeneic hematopoietic cell transplantation: From definition to mechanism-based management

Poor graft function (PGF) is a serious complication after allogeneic hematopoietic cell transplantation, characterized by persistent cytopenias despite donor engraftment and associated with substantial morbidity and inferior survival. Its clinical interpretation remains challenging because of heterogeneity in diagnostic criteria and overlap with graft failure, graft rejection, mixed chimerism, relapse, infection, and treatment-related marrow suppression. Current evidence suggests that PGF may result from a complex interplay among stem cell-intrinsic defects, bone marrow microenvironment injury, inflammatory and immune dysregulation, viral reactivation, and donor-specific antibodies. These mechanisms provide a biologic framework for contemporary management. Therapeutic approaches include supportive care, correction of reversible causes, thrombopoietin receptor agonists, mesenchymal stemcell-based and niche-directed strategies, and, in selected patients, CD34 + -selected stem cell boost, which represents an important cellular therapeutic option for persistent PGF. Active infection at the time of stem cell boost has been associated with treatment failure and inferior outcomes, whereas donor-specific antibodies may represent an additional alloimmune barrier to hematopoietic recovery in selected transplant settings. This review summarizes current definitions, pathophysiologic mechanisms, diagnostic considerations, and therapeutic strategies in PGF and highlights future directions for biomarker development, standardized reporting, and mechanism-based management.