Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation

Sun, Yu‐Qian; Wang, Yu; Zhang, Xiao-Hui; Xu, Lei; Liu, Kai-Yan; Yan, Chen‐Hua; Liu, Zhaoyu; Huang, Xiao‐Jun

doi:10.1007/s00277-019-03715-w

Cited by 22 publications

(33 citation statements)

References 26 publications

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Section: Risk Factorsmentioning

confidence: 99%

“… 26 In secondary PGF, CMV reactivation is also an independent risk factor (HR = 7.827; 95% CI: 2.002–30.602; p = 0.003). 9 Human herpesvirus 6 (HHV-6) is closely related to human cytomegalovirus and can affect over 90% of healthy individuals during childhood. 27 It is recognized in 30% to 60% allo-HSCT recipients, especially in those of unrelated cord blood graft.…”

Section: Risk Factorsmentioning

confidence: 99%

“…3 In addition, a retrospective study focused on secondary PGF also suggested that the low (<median) CD34 + cell dose is an independent risk factor [hazard ratio (HR) = 3.07; 95% CI: 1.207 -7.813; p = 0.019]. 9 DSA against the unshared haplotype in the recipient is reportedly associated with an increased risk of engraftment failure in unrelated donor transplantation and haploidentical-HSCT. 10,11 Moreover, a very recent study conducted by our colleagues suggested that DSA is the only risk factor for engraftment failure (OR = 34.0; 95% CI: 2.648-436.545; p = 0.007).…”

Section: Risk Factorsmentioning

confidence: 99%

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

Chen

Wang

Zhou

et al. 2020

Therapeutic Advances in Hematology

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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.

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Section: Risk Factorsmentioning

confidence: 99%

Section: Risk Factorsmentioning

confidence: 99%

Section: Risk Factorsmentioning

confidence: 99%

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

Chen

Wang

Zhou

et al. 2020

Therapeutic Advances in Hematology

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“…Previous studies by Ciurea et al (85) showed that patients with high donor-specific anti-HLA antibody (DSA) levels (>5,000 MFI) and complement-binding DSA antibodies (C1q positive) experienced higher risk of primary graft failure. Our data demonstrated that a number of risk factors, such as infused CD34 + cells, DSA, GVHD, and CMV infection, were associated with PGF (86, 87). The available therapeutic strategies for PGF patients include the administration of hematopoietic growth factors, donor lymphocyte infusion (30), a second allo-HSCT, a CD34 + cell boost (29, 30), or mesenchymal stem cell (MSC) infusion (80, 88).…”

Section: Recent Advances In the Beijing Protocolmentioning

confidence: 65%

Granulocyte Colony-Stimulating Factor-Primed Unmanipulated Haploidentical Blood and Marrow Transplantation

2019

Self Cite

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Granulocyte colony-stimulating factor (G-CSF), a growth factor for neutrophils, has been successfully used for stem cell mobilization and T cell immune tolerance induction. The establishment of G-CSF-primed unmanipulated haploidentical blood and marrow transplantation (The Beijing Protocol) has achieved outcomes for the treatment of acute leukemia, myelodysplastic syndrome, and severe aplastic anemia with haploidentical allografts comparable to those of human leukocyte antigen (HLA)-matched sibling donor transplantation. Currently, G-CSF-mobilized bone marrow and/or peripheral blood stem cell sources have been widely used in unmanipulated haploidentical transplant settings. In this review, we summarize the roles of G-CSF in inducing T cell immune tolerance. We discuss the recent advances in the Beijing Protocol, mainly focusing on strategies that have been used to improve transplant outcomes in cases of poor graft function, virus infections, and relapse. The application of G-CSF-primed allografts in other haploidentical modalities is also discussed.

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“…For an in-depth discussion of the impacts of donor and host variables on the kinetics of immune recovery the reader is referred to excellent recent reviews [3,9]. Studies assessing the impact of the magnitude and speed of immune recovery on allo-HSCT outcomes are mostly retrospective cohort analyses from single centers and are thus subject to variations in clinical practice, such as conditioning regimens, HSC dose, GVHD prophylaxis, ex vivo HSC manipulation [3, 10,11]. Nevertheless, interesting insights into recovery of adaptive and innate immunity have been obtained and are summarized in Table 1.…”

Section: The Importance Of Post-allo-hsct Immune Reconstitution Kineticsmentioning

confidence: 99%

Associations between the Gut Microbiota, Immune Reconstitution, and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation

Fiorenza

Turtle

2021

Immunometabolism

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Immune reconstitution following allogeneic hematopoietic stem cell transplantation (allo-HSCT) sets the stage for the goal of a successful transplant—the prevention of disease relapse without graft versus host disease (GVHD) and opportunistic infection. In both epidemiologic studies and in controlled animal studies, it is known that the gut microbiome (GM) can profoundly influence normal innate and adaptive immune development and can be altered by microbial transfer and antibiotics. Following allo-HSCT the GM has been shown to influence clinical outcomes but published associations between the GM and immune reconstitution post-allo-HSCT are lacking. In this viewpoint we propose that the extensive knowledge garnered from studying normal immune development can serve as a framework for studying immune development post-allo-HSCT. We summarize existing studies addressing the effect of the GM on immune ontogeny and draw associations with immune reconstitution and the GM post-allo-HSCT.

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Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation

Cited by 22 publications

References 26 publications

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

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

Granulocyte Colony-Stimulating Factor-Primed Unmanipulated Haploidentical Blood and Marrow Transplantation

Associations between the Gut Microbiota, Immune Reconstitution, and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation

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