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.

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

“…Widely proposed is the “seed, soil and climate” model for the pathophysiology of PGF ( 6 , 29 ). Current literature suggests hematopoietic stem cells (seed) abnormalities have a causative role in PGF.…”

“…However, hematologists have noticed that even if the patients achieved initial hematopoietic reconstitution and maintain complete donor-originated hematopoietic cells, they may develop intractable multilineage cytopenia afterwards ( 4 , 5 ). This is defined as secondary poor graft function (sPGF), and it occurs in 5-27% of post-transplantation cases ( 6 ). Patients with sPGF lose their initial hematopoietic reconstitution, which leads to increased risks of severe infection, major bleeding events, and other life-threatening complications after transplantation.…”

“…Studies have reported several risk factors for sPGF. Cytomegalovirus (CMV) reactivation and graft-versus-host disease (GvHD) are the two most recognized risk factors ( 6 ). Other potential risk factors include haplo-HSCT setting, recipient age, conditioning regimen, Epstein-Barr virus (EBV) infection, etc.…”

Non-relapse cytopenias following allogeneic stem cell transplantation, a case based review

“…2b, c. These cases demonstrate PGF which has been reviewed in detail previously [34] and will be used to frame a discussion regarding pathophysiology and potential treatments.…”

Medication Regularity of Traditional Chinese Medicine in the Treatment of Aplastic Anemia Based on Data Mining

“…A study conducted by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT) showed that graft-versus-host disease-free, relapse-free survival (GRFS) of allo-HSCT for AA was only 69% over 5 years [ 9 ]. However, the remaining patients still have complications, such as graft-versus-host disease (GVHD) [ 10 ], virus infection [ 11 ], poor graft function [ 12 ], and so on. Although the treatment of AA in Western medicine is developing rapidly, there are still many nonnegligible clinical symptoms.…”