Immunological heterogeneity of healthy peripheral blood stem cell donors – preharvesting donor characteristics, additional heterogeneity induced by granulocyte colony-stimulating factor and possible importance for outcome after allotransplantation

Bruserud, Øystein; Melve, Guro Kristin; Gedde‐Dahl, Tobias; Tvedt, Tor Henrik Anderson

doi:10.1080/17474086.2018.1511420

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…First, pretransplant recipient characteristics are associated with outcomes after allotransplantation [480,481]. Second, donor and graft characteristics are also associated with prognosis [482,483]. Finally, the use of G-CSF therapy to support posttransplant engraftment has an adverse prognostic impact, especially for patients receiving conditioning therapy, including total body irradiation [484,485].…”

Section: Expected Immune Reconstitution After Allogeneic Stem Cell Trmentioning

confidence: 99%

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Rundgren

Bruserud

Ryningen

et al. 2018

Journal of Immunological Methods

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Section: Expected Immune Reconstitution After Allogeneic Stem Cell Trmentioning

confidence: 99%

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Rundgren

Bruserud

Ryningen

et al. 2018

Journal of Immunological Methods

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“…Signs of inflammation are associated with an adverse prognosis after allogeneic stem cell transplantation [ 13 ], and signs of inflammation are also common in MDS [ 65 ]. Differences in inflammatory regulation may also contribute to the advantage of using younger matched unrelated donors instead of matched sibling donors in elderly AML patients [ 66 , 67 ]. Furthermore, the effect of pretransplant ATG on non-relapse mortality seems to differ between patients with MDS and other hematological malignancies, an observation suggesting that the pretransplant immunobiology of MDS patients is different [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Pretransplant Systemic Lipidomic Profiles in Allogeneic Stem Cell Transplant Recipients

Hatfield

Bruserud

Reikvam

2022

Cancers

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Allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies. However, this treatment is associated with severe treatment-related morbidity and mortality. The metabolic status of the recipient may be associated with the risk of development of transplant-associated complications such as graft-versus-host disease (GVHD). To better understand the impact of the lipidomic profile of transplant recipients on posttransplant complications, we evaluated the lipid signatures of patients with hematological disease using non-targeted lipidomics. In the present study, we studied pretransplant serum samples derived from 92 consecutive patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). A total of 960 lipid biochemicals were identified, and the pretransplant lipidomic profiles differed significantly when comparing patients with and without the risk factors: (i) pretransplant inflammation, (ii) early fluid overload, and (iii) patients with and without later steroid-requiring acute GVHD. All three factors, but especially patients with pretransplant inflammation, were associated with decreased levels of several lipid metabolites. Based on the overall concentrations of various lipid subclasses, we identified a patient subset characterized by low lipid levels, increased frequency of MDS patients, signs of inflammation, decreased body mass index, and an increased risk of early non-relapse mortality. Metabolic targeting has been proposed as a possible therapeutic strategy in allotransplant recipients, and our present results suggest that the clinical consequences of therapeutic intervention (e.g., nutritional support) will also differ between patients and depend on the metabolic context.

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“…Previous studies suggest that healthy stem cell donors are heterogeneous with regard to the effects of G-CSF on donor immunoregulation and the number, as well as the functional status, of immunocompetent graft cells [ 9 , 13 , 15 , 18 , 19 , 20 , 21 ]. One of these studies even suggests that G-CSF induced donor heterogeneity is important for outcome after allotransplantation [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…As described in a recent article, several studies have now described associations between graft compositions and outcome after ALLO-SCT [ 16 ], and the first study of individualized GVHD prophylaxis based on graft composition has already been published [ 17 ]. However, several studies have demonstrated that the immunomodulatory effects of G-CSF-induced stem cell mobilization differ between healthy donors [ 18 ]. Firstly, the effects of G-CSF on serum levels of a wide range of both pro- and anti-inflammatory cytokines, as well as soluble adhesion molecules and extracellular proteases, differ between healthy donors [ 9 , 19 ]; Secondly, the effect of G-CSF on immunoregulatory metabolites also varies [ 13 ]; Thirdly, the numbers of different immunocompetent cell subsets vary between grafts derived from different donors [ 20 ]; Finally, a recent study suggests that the responsiveness of immunocompetent cells to G-CSF administration differs between healthy donors, i.e., there are qualitative differences, and not only quantitative differences, between grafts derived from different donors [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Immunological Heterogeneity of Healthy Peripheral Blood Stem Cell Donors—Effects of Granulocyte Colony-Stimulating Factor on Inflammatory Responses

Tvedt

Melve

Tsykunova

et al. 2018

IJMS

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Interleukin-6 (IL-6) contributes to the development of immune-mediated complications after allogeneic stem cell transplantation. However, systemic IL-6 levels also increase during granulocyte colony-stimulating factor (G-CSF) mobilization of hematopoietic stem cells in healthy donors, but it is not known whether this mobilization alters systemic levels of other IL-6 family cytokines/receptors and whether such effects differ between donors. We examined how G-CSF administration influenced C-reactive protein (CRP) levels (85 donors) and serum levels of IL-6 family cytokines/receptors (20 donors). G-CSF increased CRP levels especially in elderly donors with high pretherapy levels, but these preharvesting levels did not influence clinical outcomes (nonrelapse mortality, graft versus host disease). The increased IL-6 levels during G-CSF therapy normalized within 24 h after treatment. G-CSF administration did not alter serum levels of other IL-6-familly mediators. Oncostatin M, but not IL-6, showed a significant correlation with CRP levels during G-CSF therapy. Clustering analysis of mediator levels during G-CSF administration identified two donor subsets mainly characterized by high oncostatin M and IL-6 levels, respectively. Finally, G-CSF could increase IL-6 release by in vitro cultured monocytes, fibroblasts, and mesenchymal stem cells. In summary, G-CSF seems to induce an acute phase reaction with increased systemic IL-6 levels in healthy stem cell donors.

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Immunological heterogeneity of healthy peripheral blood stem cell donors – preharvesting donor characteristics, additional heterogeneity induced by granulocyte colony-stimulating factor and possible importance for outcome after allotransplantation

Cited by 5 publications

References 15 publications

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

Pretransplant Systemic Lipidomic Profiles in Allogeneic Stem Cell Transplant Recipients

Immunological Heterogeneity of Healthy Peripheral Blood Stem Cell Donors—Effects of Granulocyte Colony-Stimulating Factor on Inflammatory Responses

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