Larger numbers of CD4bright dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation

Waller, Edmund K.; Rosenthal, Hilary; Jones, Terry W.; Peel, Jennifer L.; Lonial, Sagar; Langston, Amelia; Redei, Istvan; Jurickova, Ingrid; Boyer, Michael W.

doi:10.1182/blood.v97.10.2948

Cited by 125 publications

(81 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A more interesting speculation may be drawn from observations of Chaperot et al 10 who demonstrated that cultured leukemic cells of CD4 þ CD56 þ hematodermic neoplasms can manifest plasmacytoid dendritic cell-like immunologic properties, including upregulation of costimulatory molecules and antigen presentation to T cells. The ability of BDCA-2 expressing plasmacytoid dendritic cells to induce Th2 immunity and the association of donor plasmacytoid dendritic cells with decreased allo-reactivity of donor T-cells after allogeneic bone marrow transplantation 26 suggest the hypothesis that the CD4 þ CD56 þ malignant counterpart of plasmacytoid dendritic cell may have capacity for antigen presentation and ability to induce Th2 and anergic immune responses in vivo. In short, these properties could yield decreased antitumor immune responses in patients with BDCA-2-positive, TdT-negative 'more mature' tumors that are induced by the tumor itself.…”

Section: Discussionmentioning

confidence: 99%

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms

et al. 2006

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms

et al. 2006

View full text Add to dashboard Cite

“…9 Therefore, it appears very important that future studies may address the question of whether DC2 included in the graft, as well as DC2 recovery after allogeneic transplantation of hematopoietic stem cells, may correlate with hematological and immunological reconstitution, infectious events, GVHD or graft rejection episodes after transplant. For example, an initial study by Waller et al 15 suggested that a higher content of CD3 Ϫ CD4 bright DC2 in the graft would correlate with chronic GVHD and relapse after allogeneic bone marrow transplant. Monitoring of circulating DC2 numbers might also be of clinical importance in settings other than HSCT, as recently proposed for HIV patients.…”

Section: Discussionmentioning

confidence: 99%

Use of anti-BDCA-2 antibody for detection of dendritic cells type-2 (DC2) in allogeneic hematopoietic stem cell transplantation

Arpinati

Chirumbolo

Urbini

et al. 2002

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:TH2-inducing dendritic cells (DC2) are commonly identified as negative for lineage markers and positive for HLA-DR and CD123 expression. More recently, normal blood DC2 were shown also to be positive for BDCA-2 and BDCA-4 antigens. The aim of this study was to evaluate whether BDCA-2 expression on DC2 is impaired in patients undergoing an allogeneic hematopoietic stem cell transplantation (HSCT) and in healthy donors treated with G-CSF for HSC mobilization. Flow cytometry assays for DC2 detection using either a triple staining with anti-HLA-DR PerCP, anti-Lin ؉ anti-CD34 FITC and anti-CD123 PE monoclonal antibodies (mAbs), or a double staining with anti-HLA-DR PE and anti-BDCA-2 FITC mAbs were compared in blood samples from patients who underwent an allogeneic HSCT (n ‫؍‬ 30) or from healthy donors before (n ‫؍‬ 11) and after (n ‫؍‬ 8) G-CSF mobilization, as well as in healthy donors' leukapheresis products (n ‫؍‬ 12) or bone marrow (n ‫؍‬ 4). Staining of BDCA-2 + cells with other markers such as anti-CD38, anti-CD54 and anti-CD58 were also performed. Median values of CD123 ؉ DC2 and BDCA-2 ؉ DC2 were not statistically different in the blood of patients previously treated with chemotherapy, nor in the blood or bone marrow of heathy donors. Also, a 5 day G-CSF treatment did not affect BDCA-2 or adhesion molecule expression on healthy donors' blood DC2 significantly. A correlation between all the results (n ‫؍‬ 65) obtained with the two assays was demonstrated in a linear regression curve (r ‫؍‬ 0.914) (P ‫؍‬ 0.00001). BDCA-2 is a marker highly specific for DC2 that is not downregulated by chemotherapy or G-CSF treatment. Therefore, the anti-BDCA-2 mAb can be efficiently combined with other mAbs and used in studies addressing the role of DC2 in the allogeneic HSCT setting.

show abstract

“…[42][43][44] Lonial et al 45 recently reported slower T-cell recovery in patients receiving higher numbers of G-CSF-mobilized pDCs within the graft; further, high content of DCs in BM graft, but not in PBSC, have been associated with increased incidence of disease relapse. 46 These data have raised the concern that DC-mediated G-CSF action on mobilized T cells could impair their anti-leukemic activity. However, mobilized lymphocytes maintain their GVL effect via different pathways, 47 and Abbi et al 48 recently showed that G-CSF-mobilized donor lymphocyte infusions possess similar therapeutic activity compared with conventional unmobilized donor lymphocyte infusions.…”

Section: Allogeneic Graft Immune Cell Subsets and Tolerancementioning

confidence: 99%

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Saraceni

Shem‐Tov

Olivieri

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34 + stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34 + /CD38 − stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant.

show abstract

Larger numbers of CD4bright dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation

Abstract: Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34 ؉ cells influence relapse and event-free survival (EFS) after BMT.

Cited by 125 publications

References 41 publications

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms

Use of anti-BDCA-2 antibody for detection of dendritic cells type-2 (DC2) in allogeneic hematopoietic stem cell transplantation

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Contact Info

Product

Resources

About