TY - JOUR
T1 - Graft-versus-host disease of the skin
T2 - Life and death on the epidermal edge
AU - Hofmeister, Craig C.
AU - Quinn, Adam
AU - Cooke, Kenneth R.
AU - Stiff, Patrick
AU - Nickoloff, Brian
AU - Ferrara, James L.M.
N1 - Funding Information:
Supported by National Institutes of Health grants no. P01 CA 39542 and R01 AR47814. J.L.M.F. is a Doris Duke Distinguished Clinical Scientist; K.R.C. is an Amy Strelzer-Manasevit Scholar of the National Marrow Program, a Fellow of the Robert Wood Johnson Medical Minority Faculty Development Program, and the recipient of a Translational Research Award from the Leukemia and Lymphoma Society.
PY - 2004/6
Y1 - 2004/6
N2 - Despite impressive advances in the field of allogeneic hematopoietic transplantation, graft versus host disease (GVHD) remains a significant obstacle to be overcome; it would enhance the safety and efficacy of this life-saving therapy. This review provides a framework for understanding the molecular and cellular basis underlying GVHD. We propose a 3-phase model of GVHD that highlights the importance of the conditioning regimen on the recipient tissues administered prior to infusion of donor bone marrow inoculum. A novel skin explant model, designed to take into consideration the immunobiological consequences of conditioning regimens on resident host cells, is proposed to advance our understanding of GVHD and serve as a potential prognostic tool when allogeneic recipient/donor combinations are being contemplated in the clinic. Within this review, specific emphasis is placed on the importance of defining the apoptotic machinery engaged in epidermal keratinocytes triggered by both conditioning regimens, and by host resident and recruited immunocytes and soluble mediators produced at sites of injury. The review is completed with a working model for cutaneous GVHD. Although the skin is highlighted because of its accessibility for clinical observations and serial sampling opportunities, lessons learned from studies of cutaneous GVHD are likely to provide valuable insights into GVHD occurring in the gastrointestinal tract, lung, and liver. With new insights designed to better predict and prevent GVHD and novel agents designed to treat GVHD, overcoming this current impediment to successful bone marrow transplantation should become increasingly feasible.
AB - Despite impressive advances in the field of allogeneic hematopoietic transplantation, graft versus host disease (GVHD) remains a significant obstacle to be overcome; it would enhance the safety and efficacy of this life-saving therapy. This review provides a framework for understanding the molecular and cellular basis underlying GVHD. We propose a 3-phase model of GVHD that highlights the importance of the conditioning regimen on the recipient tissues administered prior to infusion of donor bone marrow inoculum. A novel skin explant model, designed to take into consideration the immunobiological consequences of conditioning regimens on resident host cells, is proposed to advance our understanding of GVHD and serve as a potential prognostic tool when allogeneic recipient/donor combinations are being contemplated in the clinic. Within this review, specific emphasis is placed on the importance of defining the apoptotic machinery engaged in epidermal keratinocytes triggered by both conditioning regimens, and by host resident and recruited immunocytes and soluble mediators produced at sites of injury. The review is completed with a working model for cutaneous GVHD. Although the skin is highlighted because of its accessibility for clinical observations and serial sampling opportunities, lessons learned from studies of cutaneous GVHD are likely to provide valuable insights into GVHD occurring in the gastrointestinal tract, lung, and liver. With new insights designed to better predict and prevent GVHD and novel agents designed to treat GVHD, overcoming this current impediment to successful bone marrow transplantation should become increasingly feasible.
KW - Apoptosis
KW - Conditioning regimens
KW - Cytokine storm
KW - Dendritic (antigen presenting) cells
KW - Skin explant assay
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U2 - 10.1016/j.bbmt.2004.03.003
DO - 10.1016/j.bbmt.2004.03.003
M3 - Article
C2 - 15148490
AN - SCOPUS:2442417361
VL - 10
SP - 366
EP - 372
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 6
ER -