Clinical features, pathophysiology and therapy of Poor Graft Function Post Allogeneic Stem Cell Transplantation

Abstract

Poor graft function (PGF) defined by the presence of multi-lineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (alloSCT). Inducers or potentiators of allo-immunity such as CMV reactivation and graft versus host disease (GVHD) are associated with the development of PGF, however more clinical studies are required to establish further risk factors and describe outcomes of PGF. The pathophysiology of PGF can be conceptualized as dysfunction related to the number or productivity of the stem cell compartment, defects in bone marrow microenvironment components such as mesenchymal stromal cells and endothelial cells, or immunological suppression of post alloSCT haematopoiesis. Treatment strategies focused on improving stem cell number and function and microenvironment support of haematopoiesis have been attempted with variable success. There has been limited use of immune manipulation as a therapeutic strategy, but emerging therapies hold promise. This review details the current understanding of the causes of PGF and methods of treatment to provide a framework for clinicians managing this complex problem.