Evaluation of risk factors for and subsequent mortality from poor graft function (PGF) post allogeneic stem cell transplantation

Prabahran, Ashvind; Koldej, Rachel; Chee, Lynette; Wong, Eric; Ritchie, David

doi:10.1080/10428194.2021.1872072

Cited by 13 publications

(17 citation statements)

References 30 publications

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“…CMV inhibits hematopoiesis directly by infecting bone marrow or suppress hematopoiesis indirectly through the infection of stromal cells ( 34 , 35 ). Previous studies ( 7 , 23 , 36 ) have identified CMV viremia as an independent risk factor for sPGF. It is reported that recipients undergoing haplo-HSCT have a higher incidence of CMV reactivation, as well as refractory CMV viremia ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 86%

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

et al. 2022

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Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.

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Section: Discussionmentioning

confidence: 86%

“…The occurrence of aGvHD has also been accepted as contributing to the development of sPGF ( 36 , 40 ). In this study, we found a marginal association between grade 3-4 aGvHD and sPGF.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Regarding outcomes, although many publications presented demonstrate heterogenous outcomes following establishment of PGF, a recent study by our group showed that patients who did not recover marrow function had a 2-year overall survival (OS) of 6%. 9 Outside of PGF-specific publications, there are numerous retrospective studies evaluating risk factors for “graft failure” defined by a variety of terms including neutropenia or thrombocytopenia irrespective of level of donor chimerism. 2,3 This definition of “graft failure” would encompass patients with PGF; splenomegaly, CMV infection, multiorgan dysfunction due to sepsis, as well as low stem cell dose have been found as possible associations.…”

Section: Risk Factors For the Development Of Pgf And Clinical Outcome...mentioning

confidence: 99%

“…Indeed, in our study, we demonstrated that a platelet count of ≤60 × 10 9 /L or hemoglobin (Hb) <80 g/L was associated with mortality after establishment of PGF. 9 To resolve the question of whether depth vs duration of cytopenias is important in deciding when to treat PGF, further prospective studies evaluating clinical or biomarker-based associations with poor outcome would be useful to determine who will not improve without intervention.…”

Section: Risk Factors For the Development Of Pgf And Clinical Outcome...mentioning

confidence: 99%

Clinical features, pathophysiology, and therapy of poor graft function post–allogeneic stem cell transplantation

et al. 2022

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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.

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“…In a prospective study, approximately 15% of patients with severe aplastic anemia (AA) who underwent haplo-SCT developed primary PGF ( 8 ). Primary PGF shows a very poor prognosis, with a 1-year overall survival (OS) rate of 25.0% ( 5 ) and 2-year OS of 6% in patients without hematopoietic recovery ( 9 ). Because of persistent leukocytopenia and thrombocytopenia, PGF is often accompanied by complications such as infection and bleeding, thus increasing the mortality rate.…”

Section: Introductionmentioning

confidence: 99%

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

Man

Yao

et al. 2022

Front. Immunol.

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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.

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Evaluation of risk factors for and subsequent mortality from poor graft function (PGF) post allogeneic stem cell transplantation

Cited by 13 publications

References 30 publications

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

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

Clinical features, pathophysiology, and therapy of poor graft function post–allogeneic stem cell transplantation

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

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