Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation

Rommeley, Maraike; Spies-Weisshart, Baerbel; Schilling, K; Hochhaus, Andreas; Sayer, Herbert G.; Scholl, Sebastian

doi:10.1007/s00432-011-0989-x

Cited by 15 publications

(16 citation statements)

References 24 publications

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“…Conversely, iMs tended to be higher in PB of patients compared to healthy donors. Of note, while the latter observation seems to be in agreement with data from other authors , no information is currently available about the kinetics of reconstitution of ncMs, as defined by our analysis .…”

Section: Discussionsupporting

confidence: 92%

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Mimiola

Marini

Perbellini

et al. 2014

Clinical and Experimental Immunology

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SummaryThe role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.

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Section: Discussionsupporting

confidence: 92%

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Mimiola

Marini

Perbellini

et al. 2014

Clinical and Experimental Immunology

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“…28 Additionally, the improved recovery of CD14 þ CD16 þ monocytes post allogeneic HSCT has recently been associated with less extensive chronic GVHD. 29 Our findings are limited in that we did not have blood samples available for subset analysis or functional testing, but potential cellular predictors of subsequent chronic GVHD and its treatment would be of significant clinical utility.…”

Section: Discussionmentioning

confidence: 94%

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

DeCook

Thoma

Huneke

et al. 2012

Bone Marrow Transplant

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We have recently shown that lymphocyte and monocyte recovery by day þ 100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days þ 15, þ 30, þ 60 and þ 100 with the outcomes. Multivariate analysis revealed that day þ 100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P ¼ 0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P ¼ 0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, Po0.001). No patient in cluster C had a day þ 100 AMC 4300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day þ 100 post fludarabine/melphalanconditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

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“…In contrast, non-classical monocytes secrete substantial levels of inflammatory cytokines (TNF and interleukin [IL]-1β) and are known to exert endothelial surveillance by endovascular slow patrolling when tissue damage is present [14]. These roles make monocytes a critical cell line for host defense against common post-HCT infections including Aspergillus , and for mitigating the risk of developing GVHD [15-22].…”

Section: Introductionmentioning

confidence: 99%

Monocyte reconstitution and gut microbiota composition after hematopoietic stem cell transplantation

Morjaria

Zhang

Kim

et al. 2019

Preprint

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Monocytes are an essential cellular component of the innate immune system that support the 33 host's effectiveness to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) 34 results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations 35 are not fully understood. In this study, we investigated whether the composition of the gastrointestinal 36 microbiota is associated with the recovery of monocyte homeostasis after HCT. 37 38 Methods: 39We performed a single-center, prospective, pilot study of 18 recipients of either autologous or 40 allogeneic HCT. Serial blood and stool samples were collected from each patient during their HCT 41 hospitalization. Analysis of the gut microbiota was done using 16S rRNA gene sequencing and flow 42 cytometric analysis was used to characterize the phenotypic composition of monocyte populations. 4344 Results: 45Dynamic fluctuations in monocyte reconstitution occurred after HCT and large differences were 46 observed in monocyte frequency among patients over time. Recovery of absolute monocyte counts and 47 monocyte subsets showed significant variability across the heterogeneous transplant types and 48 conditioning intensities; no relationship to the microbiota composition was observed in this small 49 cohort. 51 Conclusion: 52A relationship between the microbiota composition and monocyte homeostasis could not be 53 firmly established in this pilot study.3 54 55 cell transplantation (HCT) is a potentially curative procedure for patients with 81 hematologic malignancies but its success has been limited by the morbidity and mortality of post-82 transplant infections and relapse. Impaired immune reconstitution post-HCT increases the risk of both of 83 these complications [1][2][3][4]. Multiple factors influence the vulnerability of patients to these complications 84 including: time since transplantation, graft source (i.e., autologous (auto-HCT) or allogeneic (allo-HCT)), 85 and persisting myelosuppression (humoral and cell-mediated) post-HCT [2, 3]. Alterations in the 86 microbiome have been associated with clinical outcomes of patients who have undergone HCT, 87 including their survival. However, the mechanisms by which the gut microbiota exerts its effects, both 88 beneficial and detrimental, have not been fully elucidated [5, 6]. 89In humans there are three main circulating monocyte subsets with diverse functions, classified 90 based on their expression of CD14 and CD16 surface proteins and cytokine production. These monocyte 91 subsets are named "classical", "intermediate", and "non-classical monocytes" [7-9] and typically 92 comprise 85%, 10%, and 5% respectively of the circulating monocyte pool in a healthy individual under 93 homeostatic conditions [10, 11]. Classical monocytes specialize in phagocytosis and produce the 94 cytokine IL-10 [12], while intermediate monocytes have elevated surface expression of MHC class II, 95 suggesting they have an important role in antigen presentation [13]. In contrast, non-c...

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Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation

Cited by 15 publications

References 24 publications

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

Monocyte reconstitution and gut microbiota composition after hematopoietic stem cell transplantation

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