TY  - JOUR
AU  - Kariminia, A
AU  - Ivison, S
AU  - Ng, B
AU  - Rozmus, J
AU  - Sung, S
AU  - Varshney, A
AU  - Aljurf, M
AU  - Lachance, S
AU  - Walker, I
AU  - Toze, C
AU  - Lipton, J
AU  - Lee, SJ
AU  - Szer, J
AU  - Doocey, R
AU  - Lewis, I
AU  - Smith, C
AU  - Chaudhri, N
AU  - Levings, MK
AU  - Broady, R
AU  - Devins, G
AU  - Szwajcer, D
AU  - Foley, R
AU  - Mostafavi, S
AU  - Pavletic, S
AU  - Wall, DA
AU  - Couban, S
AU  - Panzarella, T
AU  - Schultz, KR
Y2  - 2020/12/21
Y1  - 2017/11/01
SN  - 0390-6078
UR  - http://hdl.handle.net/11343/257113
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 filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright 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 CD56bright 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 CD56bright 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.
LA  - English
PB  - FERRATA STORTI FOUNDATION
T1  - CD56(bright) natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results
DO  - 10.3324/haematol.2017.170928
IS  - Haematologica: the hematology journal
VL  - 102
IS  - 11
SP  - 1936-1946
L1  - /bitstream/handle/11343/257113/PMC5664398.pdf?sequence=1&isAllowed=y
ER  -