Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

Abstract

The aim of this study was to investigate the effects of natural killer (NK) cells on transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors. Forty-one haploidentical allogeneic hematopoietic SCT patients were analyzed according to the NK cell concentration in relation to acute GVHD (aGVHD), chronic GVHD (cGVHD), TRM and leukemia-free survival. The patients receiving a higher dose of CD56 bright NK cells (41.9 Â 10 6 /kg) showed a higher incidence of grades II-IV aGVHD (hazard risk (HR), 2.872; P ¼ 0.022) and cGVHD (HR, 2.884; P ¼ 0.039). A higher CD56 dim /CD56 bri NK cell ratio (48.0) was correlated with a decreased risk of III-IV aGVHD (HR, 0.290; P ¼ 0.065) and TRM (HR, 0.072; P ¼ 0.012), thereby increasing the rate of leukemia-free survival (HR, 0.174; P ¼ 0.007) after haploidentical transplantation without in vitro T-cell depletion. Our results suggest that a high allograft CD56 dim /CD56 bright NK cell ratio (48.0) plays an important role in improving transplant outcomes. A higher dose of CD56 bright NK cells might be a predictor for a higher incidence of GVHD.

The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis

“…Our results suggest that different cellular compositions and immunological effects exist between the G-BM/G-PB mixed and G-PB-only harvests. 17,18 Therefore, it is possible that differences in hematopoietic reconstitution between the G-BM/G-PB mixed and G-PB-only harvests exist, although further study is needed to confirm this.…”

Haploidentical Bone Marrow Transplantation Without T-Cell Depletion

“…15,43 Using their unmanipulated haploidentical blood and marrow transplant protocol, the Peking University group found that a higher dose of CD4 ϩ CD45RA ϩ CD62L ϩ or CD56 bright NK cells correlated with an increased incidence of grades II-IV acute GVHD while, conversely, a lower dose of CD4 ϩ CD25 high CD45RA ϩ CD62L ϩ T cells in the allografts was associated with a higher incidence of grades II-IV acute GVHD. 21,44 Other factors, including a lower CD56 dim /CD56 bright NK cell ratio (Ͻ8.0) and a higher CD4/CD8 ratio (Ͼ1.16) in the allografts, may contribute not only to higher risk of acute GVHD but also to increased TRM and decreased OS. 21,42 Recently, Huo et al 45 reported that HLA-B mismatch was an independent risk factor for acute GVHD and TRM after HLA-haploidentical transplantation without ex vivo TCD.…”

“…21,44 Other factors, including a lower CD56 dim /CD56 bright NK cell ratio (Ͻ8.0) and a higher CD4/CD8 ratio (Ͼ1.16) in the allografts, may contribute not only to higher risk of acute GVHD but also to increased TRM and decreased OS. 21,42 Recently, Huo et al 45 reported that HLA-B mismatch was an independent risk factor for acute GVHD and TRM after HLA-haploidentical transplantation without ex vivo TCD. Researchers from Japan also showed that among patients with standard-risk diseases who received transplantation from a related donor with an HLA-1 antigen mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host direction, the presence of an HLA-B antigen mismatch was significantly associated with a lower OS rate.…”

The impact of donor characteristics on the immune cell composition of second allografts in Chinese people

“…First, this is a retrospective, single‐center study. Second, some other immune cells, such as CD4 + CD25 + Foxp3 + T cells , natural killer cells and dendritic cells , were not included in this study. Third, all of the donors were Asian descent and there was no diversity.…”