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 -