Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

Abstract

Poor graft function (PGF) following allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a life-threatening complication and is characterized by bilineage or trilineage blood cell deficiency and hypoplastic marrow with full chimerism. With the rapid development of allo-HSCT, especially haploidentical-HSCT, PGF has become a growing concern. The most common risk factors illustrated by recent studies include low dose of infused CD34+ cells, donor-specific antibody, cytomegalovirus infection, graft versus host disease (GVHD), iron overload and splenomegaly, among others. Because of the poor prognosis of PGF, it is crucial to uncover the underlying mechanism, which remains elusive. Recent studies have suggested that the bone marrow microenvironment may play an important role in the pathogenesis of PGF. Deficiency and dysfunction of endothelial cells and mesenchymal stem cells, elevated reactive oxygen species (ROS) levels, and immune abnormalities are believed to contribute to PGF. In this review, we also discuss recent clinical trials that evaluate the safety and efficacy of new strategies in patients with PGF. CD34+-selected stem-cell boost (SCB) is effective with an acceptable incidence of GVHD, despite the need for a second donation. Alternative strategies including the applications of mesenchymal stem cells, N-acetyl-l-cysteine (NAC), and eltrombopag have shown favorable outcomes, but further large-scale studies are needed due to the small sample sizes of the recent clinical trials.

Addition of a Single Low Dose of Anti T-Lymphocyte Globulin to Post-Transplant Cyclophosphamide after Allogeneic Hematopoietic Stem Cell Transplant: A Pilot Study

“…Neutrophil engraftment was defined as achievement of an absolute polymorphonuclear leukocyte count above 500 cells/µL for 3 consecutive days. Poor graft function was defined as a bi-or tri-lineage cytopenia after day 28 in the presence of full donor hypoplastic marrow and of disease remission [19]. We collected data on chimerism data measured through real-time quantitative polymerase chain reaction on bone marrow samples performed around day 30 for patients with disease remission [20].…”

Exploring the Potential of Eltrombopag: Room for More?

“…PGF occurs in up to 20% of patients; it is defined by the presence of persistent cytopenias (mainly thrombocytopenia) after completion of allo-HSCT procedures. The physiopathology of PGF is not fully understood; factors such as the graft composition, HLA mismatches, conditioning regimen and immunosuppression, graft versus host disease (GvHD), post-transplant infections and viral reactivations are implicated in the PGF pathogenesis ( Chen et al, 2020 ).…”

“…Notably, ELT efficacy seems to be irrespective of the putative PGF cause ( Marotta et al, 2019 ). It is noteworthy that ELT is capable of inhibiting human cytomegalovirus (CMV) replication through its iron chelation properties ( Vogel et al, 2019 ); this is of great importance, considering that CMV reactivation is one of the most typical causes of PGF ( Chen et al, 2020 ).…”

The frequency of poor engraftment after allogeneic hematopoietic stem cell transplantation

“…Slabost kalema se manifestuje kao pancitopenija sa potpunim donorskim himerizmom (slaba funkcija kalema -poor graft function (PGF)), pancitopenija sa nepotpunim donorskim himerizmom (slabost kalema u užem smislu -graft failure (GF)), ili se javlja odbacivanje transplantata (graft rejection (GR)), što se manifestuje aplazijom koštane srži i/ili pancitopenijom [1][2][3].…”

“…Najčešći faktori rizika za razvoj PGF-a su: niska doza donorskih CD34+ ćelija, donor specifična antitela (DSA), citomegalovirusna (CMV) infekcija, bolest kalema protiv domaćina (engl. graft versus host disease -GvHD), prevelika zasićenost gvožđem, splenomegalija, i drugi faktori [1][2][3][4][5][6][7].…”