TY - JOUR AU - Amina Kariminia, AU - Sabine Ivison, AU - Bernard Ng, AU - Jacob Rozmus, AU - Susanna Sung, AU - Avani Varshney, AU - Mahmoud Aljurf, AU - Sylvie Lachance, AU - Irwin Walker, AU - Cindy Toze, AU - Jeff Lipton, AU - Stephanie J. Lee, AU - Jeff Szer, AU - Richard Doocey, AU - Ian Lewis, AU - Clayton Smith, AU - Naeem Chaudhri, AU - Megan K. Levings, AU - Raewyn Broady, AU - Gerald Devins, AU - David Szwajcer, AU - Ronan Foley, AU - Sara Mostafavi, AU - Steven Pavletic, AU - Donna A. Wall, AU - Stephan Couban, AU - Tony Panzarella, AU - Kirk R. Schultz, PY - 2017/10/27 Y2 - 2024/03/29 TI - CD56bright 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 JF - Haematologica JA - haematol VL - 102 IS - 11 SE - Articles DO - 10.3324/haematol.2017.170928 UR - https://haematologica.org/article/view/8257 SP - 1936-1946 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. ER -