Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation

Fagnoni, Francesco; Oliviero, Barbara; Giorgiani, Giovanna; Stefano, Piero De; Dehò, Anna; Zibera, C.; Gibelli, N.; Maccario, Rita; Prada, GA Da; Zecca, Marco; Locatelli, Franco

doi:10.1182/blood-2003-07-2443

Cited by 51 publications

(41 citation statements)

References 48 publications

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“…Patients experiencing grade 0-I aGVHD could secrete significantly higher amounts of IFN-a as compared to patients with grade II-IV aGVHD (mean, 91 vs 0 pg/ml respectively; P ¼ 0.002; Figure 1b), likely highlighting the deleterious impact of corticosteroids therapy on PDC function as described previously. 21,22 As previously shown in the myeloablative allo-SCT setting, the CD34 þ stem cell dose and other lymphoid subsets infused with the allograft did not correlate with PDC recovery after RICallo-SCT. 23 Patients with a 'low' PDC recovery had also significantly decreased lymphocyte, monocyte, but not neutrophil counts in comparison with the 'high' PDC recovery group Table 2 Transplant-related events and outcome of the 'low' vs 'high' PDC recovery groups at 3 months after transplantation Nonrelapse mortality according to the 'low' vs 'high' PDCs recovery groups determined at the third month after RIC-allo-SCT.…”

Section: Resultsmentioning

confidence: 55%

“…21,22,[25][26][27][28] The results from our study suggest that quantification of PDCs at 3 months after RIC-allo-SCT (widely used date for allo-SCT patient assessment) 29 may be a simple but major indicator for long-term outcome, especially transplant-related mortality and OS. Interestingly, in patients receiving a myeloablative standard allo-SCT, Reddy et al 27 could show recently that a 'low' DC recovery (including PDCs) at the time of engraftment is associated with a worsened early outcome.…”

Section: Resultsmentioning

confidence: 90%

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Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation

et al. 2004

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Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 90%

Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation

et al. 2004

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“…21 There are reports that use of CS leads to decreased blood DC in various human disorders, including GVHD. 29,30,35,36 Since CS are usually the first choice treatment for aGVHD, it is very difficult to distinguish their influence on blood DC numbers from that of the disease. One patient in our study group, however, did not receive CS treatment despite progression of her aGVHD, and her plasmacytoid DC counts did decrease similarly to those of other patients.…”

Section: Circulating DC Numbers In the Late Post Transplant Period (4mentioning

confidence: 99%

Circulating dendritic cell subset levels after allogeneic stem cell transplantation in children correlate with time post transplant and severity of acute graft-versus-host disease

Vakkila

Thomson

Hovi

et al. 2005

Bone Marrow Transplant

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Summary:We examined the recovery of circulating monocytoid (Lin À CD11 þ HLA À DR þ ) and plasmacytoid (Lin À CD123 þ HLA À DR þ ) precursor (pre) dendritic cell (DC) subsets after allogeneic stem cell transplantation (SCT) in 39 children, using age-matched healthy children as controls. The frequencies of DCs in peripheral blood samples were determined by flow cytometry. The initial recovery of DC occurred simultaneously with myeloid engraftment. However, with time, DC subset values declined, being very low 40-50 days after SCT. Low monocytoid and plasmacytoid DC values were associated significantly with the development of severe acute graft-versus-host disease (aGVHD) (P ¼ 0.042 and 0.017, respectively). Plasmacytoid DC values were lower than in the age-matched controls for the entire follow-up period (range 102-2569 days), although, with time, values approached normal levels. Normal monocytoid DC numbers were observed within 300-400 days post SCT. The severity of chronic GVHD did not correlate with quantitative recovery of DC. We conclude that in pediatric SCT, initial recovery of DC production is concurrent with that of myelopoiesis, yet with time, DC subset values decline and low counts are associated with severe aGVHD. Monocytoid DC numbers approach normal levels within a year of SCT, but plasmacytoid DC counts recover very slowly.

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“…92 Aside from issues concerning GVHD, G-CSF may alter host defense responses to infection by preferentially inducing a Th2 response and inhibiting recovery in IL-12 production. 93 Thus, macrophage activation, immunoglobulin production, and support for CD8 þ effector T cells may be blunted, increasing susceptibility to bacterial and viral pathogens. 94 In addition to inducing chronic GVHD and immune effector cell dysfunction, cytokine mobilization may adversely effect hematopoietic stem cell engraftment.…”

Section: Recovery Of Adaptive Immunitymentioning

confidence: 99%

Immune restoration following hematopoietic stem cell transplantation: an evolving target

Auletta

Lazarus

2005

Bone Marrow Transplant

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Summary:Hematopoietic stem cell transplantation (HSCT) is the definitive cure for many malignant and nonmalignant diseases. However, delays in immune reconstitution (IR) following HSCT significantly limit the success of transplantation and increase the risk for infection and disease relapse in the transplant recipient. Therefore, ways to measure and to manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and hematopoiesis. Recent discoveries in the activation, function, and regulation of dendritic cell (DC), natural killer (NK) cell, and T-lymphocyte subtypes have been critical in developing immunotherapies used to prevent graft-versushost disease and to enhance graft-versus-leukemia. For example, regulatory T cells that induce tolerance and NK receptor-tumor ligand disparities that result in tumor lysis are being used to minimize GVHD and tumor burden, respectively. Furthermore, expansion and modulation of immune effector cells are being used to augment hematopoietic and immune recovery and to decrease transplantrelated toxicity in the transplant recipient. Specifically, DC expansion and incorporation into antitumor and antimicrobial vaccines is fast approaching application into clinical trials. This paper will review our current understanding for IR following HSCT and the novel ways in which to restore immune function and decrease transplantrelated toxicity in the transplant recipient. Bone Marrow Transplantation (2005) 35, 835-857.

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Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation

Cited by 51 publications

References 48 publications

Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation

Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation

Circulating dendritic cell subset levels after allogeneic stem cell transplantation in children correlate with time post transplant and severity of acute graft-versus-host disease

Immune restoration following hematopoietic stem cell transplantation: an evolving target

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