Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

Abstract

Poor graft function (PGF) is a life-threatening complication that occurs after transplantation and has a poor prognosis. With the rapid development of haploidentical hematopoietic stem cell transplantation, the pathogenesis of PGF has become an important issue. Studies of the pathogenesis of PGF have resulted in some success in CD34+-selected stem cell boosting. Mesenchymal stem cells, N-acetyl-l-cysteine, and eltrombopag have also been investigated as therapeutic strategies for PGF. However, predicting and preventing PGF remains challenging. Here, we propose that the seed, soil, and insect theories of aplastic anemia also apply to PGF; CD34+ cells are compared to seeds; the bone marrow microenvironment to soil; and virus infection, iron overload, and donor-specific anti-human leukocyte antigen antibodies to insects. From this perspective, we summarize the available information on the common risk factors of PGF, focusing on its potential mechanism. In addition, the safety and efficacy of new strategies for treating PGF are discussed to provide a foundation for preventing and treating this complex clinical problem.

Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis

“…Our cohort included 10 patients with monolineage severe cytopenia, and therefore was not strictly limited to patients with at least bilineage cytopenia, as suggested to be the definition of PGF by the European Society of Blood and Marrow Transplantation (EBMT) and some other experts or investigators of recent studies ( 2 – 4 , 8 , 35 , 36 ). However, in our analysis, mono- versus multiple lineage cytopenia did not appear as a factor influencing response to MSC in univariate and multivariate analyses, therefore precluding that this subgroup of patients could have influence the response rate of the overall cohort.…”

“…Although rare, PGF is a serious complication after alloHCT and coping with this condition remains a challenge for patients as they may be at increased risk of infections, bleeding events or complications related to iron overload and must undergo an increased number of hospital visits for transfusion support ( 2 , 4 , 5 , 8 ). Currently, there is no consensus on how to manage this condition.…”

“…Currently, there is no consensus on how to manage this condition. Most commonly used treatment options include growth factors such as thrombopoietin receptor agonists (TPO-RA), infusion of a donor-derived stem cell boost and second alloHCT ( 4 , 5 , 9 , 10 ). However, these options are not always feasible and could be associated with variable efficacity and toxicity.…”

“…In transplanted patients, the microenvironment of the bone marrow (BM) hematopoietic stem cell niches can be altered, as a result of damages induced by the hematological malignancy, the conditioning regimen and/or immune mediated graft-versus-host reactions ( 11 , 12 ). A dysfunctional BM microenvironment may compromise the hematopoietic functions of transplanted stem cells and contribute to the pathogenesis of PGF ( 4 , 5 , 13 ). Mesenchymal stromal cells (MSC) are multipotent progenitor cells that are a major constituent of BM hematopoietic stem cell niches.…”

Impact of iron overload on poor graft function after allo-HSCT in a patient with transfusion-dependent low-risk MDS: A case report and literature review

“…The underlying mechanism of PGF still remains unclear and the pathogenesis of PGF is probably multifactorial including immunologic issues as well as abnormalities in stem cells and the bone marrow microenvironment. [18][19][20] Accumulating evidence have shown that increased levels of reactive oxygen species (ROS) might contribute to the occurrence of PGF after allo-HSCT by impairing both HSCs and the BM microenvironment. [19,21,22] The anti-oxidant NAC can overcome the exhaustion of HSCs, improve BM endothelial cells and enhance the engraftment of HSCs by decreasing the cellular ROS levels in patients with PGF.…”