Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease.

Geoffrey W. Chan, Gullu Gorgun, Kenneth B. Miller, Francine M. Foss

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Graft-versus-host disease (GVHD) causes significant morbidity and mortality in patients undergoing allogeneic bone marrow transplantation following either a conventional or reduced-intensity preparative regimen. In a murine model, inactivation of host dendritic cells (DCs) was associated with a significant reduction in acute GVHD, suggesting that host DCs may play an important role in the pathogenesis of acute GVHD. The role of host DCs in the development of GVHD following allogeneic stem cell transplantation in humans, however, is unclear. We examined DC chimerism in patients with various hematologic malignancies who underwent a reduced-intensity preparative regimen of extracorporeal photophoresis, pentostatin, and reduced-dose total body irradiation (n = 21) or a conventional preparative regimen of cyclophosphamide and total body irradiation (n = 3). Full donor hematopoietic reconstitution was demonstrated in 19 of 21 patients who underwent a reduced-intensity preparative regimen and in all patients who underwent a conventional preparative regimen. Grade 0 to I acute GVHD and limited or no chronic GVHD were observed in 18 patients who underwent a reduced-intensity regimen and 1 patient who underwent a conventional regimen who achieved full donor DC chimerism at day +100 posttransplantation. In contrast, grade II to IV acute GVHD and extensive chronic GVHD were observed in the 2 patients who underwent a conventional regimen and the 1 patient who underwent a reduced-intensity regimen who had host rather than donor DC chimerism. The persistence of host DCs at day +100 posttransplantation is correlated with the development of severe acute and chronic GVHD (P =.001). Host DCs may represent a therapeutic target for reducing GVHD in allogeneic bone marrow transplants.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume9
Issue number3
StatePublished - Mar 2003
Externally publishedYes

Fingerprint

Cell Transplantation
Graft vs Host Disease
Dendritic Cells
Chimerism
Whole-Body Irradiation
Tissue Donors
Pentostatin
Homologous Transplantation
Stem Cell Transplantation
Hematologic Neoplasms
Bone Marrow Transplantation
Cyclophosphamide
Bone Marrow
Morbidity
Transplants
Mortality

ASJC Scopus subject areas

  • Transplantation

Cite this

Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease. / Chan, Geoffrey W.; Gorgun, Gullu; Miller, Kenneth B.; Foss, Francine M.

In: Biology of Blood and Marrow Transplantation, Vol. 9, No. 3, 03.2003, p. 170-176.

Research output: Contribution to journalArticle

Chan, Geoffrey W. ; Gorgun, Gullu ; Miller, Kenneth B. ; Foss, Francine M. / Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease. In: Biology of Blood and Marrow Transplantation. 2003 ; Vol. 9, No. 3. pp. 170-176.
@article{61dc760af9ff4f9c86fec2e0de548669,
title = "Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease.",
abstract = "Graft-versus-host disease (GVHD) causes significant morbidity and mortality in patients undergoing allogeneic bone marrow transplantation following either a conventional or reduced-intensity preparative regimen. In a murine model, inactivation of host dendritic cells (DCs) was associated with a significant reduction in acute GVHD, suggesting that host DCs may play an important role in the pathogenesis of acute GVHD. The role of host DCs in the development of GVHD following allogeneic stem cell transplantation in humans, however, is unclear. We examined DC chimerism in patients with various hematologic malignancies who underwent a reduced-intensity preparative regimen of extracorporeal photophoresis, pentostatin, and reduced-dose total body irradiation (n = 21) or a conventional preparative regimen of cyclophosphamide and total body irradiation (n = 3). Full donor hematopoietic reconstitution was demonstrated in 19 of 21 patients who underwent a reduced-intensity preparative regimen and in all patients who underwent a conventional preparative regimen. Grade 0 to I acute GVHD and limited or no chronic GVHD were observed in 18 patients who underwent a reduced-intensity regimen and 1 patient who underwent a conventional regimen who achieved full donor DC chimerism at day +100 posttransplantation. In contrast, grade II to IV acute GVHD and extensive chronic GVHD were observed in the 2 patients who underwent a conventional regimen and the 1 patient who underwent a reduced-intensity regimen who had host rather than donor DC chimerism. The persistence of host DCs at day +100 posttransplantation is correlated with the development of severe acute and chronic GVHD (P =.001). Host DCs may represent a therapeutic target for reducing GVHD in allogeneic bone marrow transplants.",
author = "Chan, {Geoffrey W.} and Gullu Gorgun and Miller, {Kenneth B.} and Foss, {Francine M.}",
year = "2003",
month = "3",
language = "English (US)",
volume = "9",
pages = "170--176",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease.

AU - Chan, Geoffrey W.

AU - Gorgun, Gullu

AU - Miller, Kenneth B.

AU - Foss, Francine M.

PY - 2003/3

Y1 - 2003/3

N2 - Graft-versus-host disease (GVHD) causes significant morbidity and mortality in patients undergoing allogeneic bone marrow transplantation following either a conventional or reduced-intensity preparative regimen. In a murine model, inactivation of host dendritic cells (DCs) was associated with a significant reduction in acute GVHD, suggesting that host DCs may play an important role in the pathogenesis of acute GVHD. The role of host DCs in the development of GVHD following allogeneic stem cell transplantation in humans, however, is unclear. We examined DC chimerism in patients with various hematologic malignancies who underwent a reduced-intensity preparative regimen of extracorporeal photophoresis, pentostatin, and reduced-dose total body irradiation (n = 21) or a conventional preparative regimen of cyclophosphamide and total body irradiation (n = 3). Full donor hematopoietic reconstitution was demonstrated in 19 of 21 patients who underwent a reduced-intensity preparative regimen and in all patients who underwent a conventional preparative regimen. Grade 0 to I acute GVHD and limited or no chronic GVHD were observed in 18 patients who underwent a reduced-intensity regimen and 1 patient who underwent a conventional regimen who achieved full donor DC chimerism at day +100 posttransplantation. In contrast, grade II to IV acute GVHD and extensive chronic GVHD were observed in the 2 patients who underwent a conventional regimen and the 1 patient who underwent a reduced-intensity regimen who had host rather than donor DC chimerism. The persistence of host DCs at day +100 posttransplantation is correlated with the development of severe acute and chronic GVHD (P =.001). Host DCs may represent a therapeutic target for reducing GVHD in allogeneic bone marrow transplants.

AB - Graft-versus-host disease (GVHD) causes significant morbidity and mortality in patients undergoing allogeneic bone marrow transplantation following either a conventional or reduced-intensity preparative regimen. In a murine model, inactivation of host dendritic cells (DCs) was associated with a significant reduction in acute GVHD, suggesting that host DCs may play an important role in the pathogenesis of acute GVHD. The role of host DCs in the development of GVHD following allogeneic stem cell transplantation in humans, however, is unclear. We examined DC chimerism in patients with various hematologic malignancies who underwent a reduced-intensity preparative regimen of extracorporeal photophoresis, pentostatin, and reduced-dose total body irradiation (n = 21) or a conventional preparative regimen of cyclophosphamide and total body irradiation (n = 3). Full donor hematopoietic reconstitution was demonstrated in 19 of 21 patients who underwent a reduced-intensity preparative regimen and in all patients who underwent a conventional preparative regimen. Grade 0 to I acute GVHD and limited or no chronic GVHD were observed in 18 patients who underwent a reduced-intensity regimen and 1 patient who underwent a conventional regimen who achieved full donor DC chimerism at day +100 posttransplantation. In contrast, grade II to IV acute GVHD and extensive chronic GVHD were observed in the 2 patients who underwent a conventional regimen and the 1 patient who underwent a reduced-intensity regimen who had host rather than donor DC chimerism. The persistence of host DCs at day +100 posttransplantation is correlated with the development of severe acute and chronic GVHD (P =.001). Host DCs may represent a therapeutic target for reducing GVHD in allogeneic bone marrow transplants.

UR - http://www.scopus.com/inward/record.url?scp=0141685067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141685067&partnerID=8YFLogxK

M3 - Article

C2 - 12652467

AN - SCOPUS:0141685067

VL - 9

SP - 170

EP - 176

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 3

ER -