TY - JOUR
T1 - CD56 bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease
T2 - The Canadian blood and marrow transplant group randomized 0601 study results
AU - Kariminia, Amina
AU - Ivison, Sabine
AU - Ng, Bernard
AU - Rozmus, Jacob
AU - Sung, Susanna
AU - Varshney, Avani
AU - Aljurf, Mahmoud
AU - Lachance, Sylvie
AU - Walker, Irwin
AU - Toze, Cindy
AU - Lipton, Jeff
AU - Lee, Stephanie J.
AU - Szer, Jeff
AU - Doocey, Richard
AU - Lewis, Ian
AU - Smith, Clayton
AU - Chaudhri, Naeem
AU - Levings, Megan K.
AU - Broady, Raewyn
AU - Devins, Gerald
AU - Szwajcer, David
AU - Foley, Ronan
AU - Mostafavi, Sara
AU - Pavletic, Steven
AU - Wall, Donna A.
AU - Couban, Stephan
AU - Panzarella, Tony
AU - Schultz, Kirk R.
N1 - Funding Information:
This study was undertaken by the CBMTG and funded by a grant from the United States National Cancer Institute (Principal Investigator: K.R. Schultz; Grant 1R01CA108752-01A2) and CBMTG. We gratefully acknowledge the recipients, donors and staff of the BMT Programs who participated in this study.
Publisher Copyright:
© 2017 Ferrata Storti Foundation.
PY - 2017/10/27
Y1 - 2017/10/27
N2 - Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastimstimulated bone marrow were grouped together, a higher chronic graftversus- host disease frequency was associated with lower proportions of CD56 bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56 bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56 bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56 bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56 bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56 bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.
AB - Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastimstimulated bone marrow were grouped together, a higher chronic graftversus- host disease frequency was associated with lower proportions of CD56 bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56 bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56 bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56 bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56 bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56 bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.
UR - http://www.scopus.com/inward/record.url?scp=85032679354&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032679354&partnerID=8YFLogxK
U2 - 10.3324/haematol.2017.170928
DO - 10.3324/haematol.2017.170928
M3 - Article
C2 - 28935847
AN - SCOPUS:85032679354
SN - 0390-6078
VL - 102
SP - 1936
EP - 1946
JO - Haematologica
JF - Haematologica
IS - 11
ER -