Michael Cuccione Childhood Cancer research Program, BC Children's Hospital, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Department of Statistics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada.
Haematologica. 2017 Nov;102(11):1936-1946. doi: 10.3324/haematol.2017.170928. Epub 2017 Sep 21.
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. .
随机试验明确表明，与未经刺激的骨髓相比，粒细胞集落刺激因子刺激的外周血造血干细胞采集作为供者来源会导致更高的慢性移植物抗宿主病发生率。加拿大血液和骨髓移植组开展了一项针对成人的 3 期研究，这些患者接受的供者来源分别为粒细胞集落刺激因子刺激的外周血造血干细胞采集或粒细胞集落刺激因子刺激的骨髓，供者均为人类白细胞抗原完全匹配的同胞。由于所有供者均接受相同的粒细胞集落刺激因子剂量方案，因此这项研究可以对干细胞来源对慢性移植物抗宿主病发生的影响进行对照评估。121 例可评估的粒细胞集落刺激因子刺激的外周血造血干细胞采集和粒细胞集落刺激因子刺激的骨髓患者供者产品通过流式细胞术进行免疫特征分析，并在移植后 2 年内检测其与急性和慢性移植物抗宿主病的相关性。评估的免疫群体包括调节性 T 细胞、中央记忆和效应 T 细胞、产生干扰素 γ的 T 细胞、不变自然杀伤 T 细胞、调节性自然杀伤细胞、树突状细胞群体、巨噬细胞、活化 B 细胞和记忆 B 细胞。当粒细胞集落刺激因子刺激的外周血造血干细胞和粒细胞集落刺激因子刺激的骨髓共同分组时，供者产品中 CD56 自然杀伤调节细胞和产生干扰素 γ的辅助性 T 细胞比例较低与更高的慢性移植物抗宿主病频率相关。较低的 CD56 自然杀伤调节细胞对粒细胞集落刺激因子刺激的外周血造血干细胞和粒细胞集落刺激因子刺激的骨髓之间广泛慢性移植物抗宿主病的发展具有不同的影响。总之，在控制粒细胞集落刺激因子对骨髓的潜在影响的情况下，我们的研究表明 CD56 自然杀伤调节细胞对粒细胞集落刺激因子刺激的外周血造血干细胞的影响比粒细胞集落刺激因子刺激的骨髓更强。这支持了这样一个结论，即 CD56 自然杀伤调节细胞比例较低导致了粒细胞集落刺激因子刺激的外周血造血干细胞采集中所见的慢性移植物抗宿主病发生率较高。
