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

• Published in: Haematologica (Roma) 2017-11, Vol.102 (11), p.1936-1946
• Main Authors: Kariminia, Amina, Ivison, Sabine, Ng, Bernard, Rozmus, Jacob, Sung, Susanna, Varshney, Avani, Aljurf, Mahmoud, Lachance, Sylvie, Walker, Irwin, Toze, Cindy, Lipton, Jeff, Lee, Stephanie J, Szer, Jeff, Doocey, Richard, Lewis, Ian, Smith, Clayton, Chaudhri, Naeem, Levings, Megan K, Broady, Raewyn, Devins, Gerald, Szwajcer, David, Foley, Ronan, Mostafavi, Sara, Pavletic, Steven, Wall, Donna A, Couban, Stephan, Panzarella, Tony, Schultz, Kirk R
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD56 Antigen - metabolism; Chronic Disease; Female; Filgrastim - pharmacology; Filgrastim - therapeutic use; Graft vs Host Disease - diagnosis; Graft vs Host Disease - etiology; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunophenotyping; Interferon-gamma - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Male; Middle Aged; Siblings; Transplantation Conditioning; Young Adult
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2017.170928

Randomized trials have conclusively shown higher rates of chronic graft- -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- -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- -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- -host disease frequency was associated with lower proportions of CD56 natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56 natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft- -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 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 natural killer regulatory cells results in the high rate of chronic graft- -host disease seen in filgrastim-stimulated apheresis peripheral blood. .