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• W3114208348 abstract "• Adaptive natural killer (NK) cells maintained stable phenotypic and functional competence beyond 2 years following haploidentical hemtopoietic cell transplantation (HCT). • Patients without disease progression had significantly better adaptive NK cell reconstitution with greater interferon gamma production. • Grafts from donors with higher adaptive NK cells had a lower risk of disease progression. • Recovery of adaptive NK cells was prompter and better in those receiving CTLA4Ig-primed donor lymphocyte infusion (DLI) compared work DLI alone. Adaptive or memory natural killer (NK) cells with epigenetic imprints similar to memory T cells have been shown to develop in response to cytomegalovirus (CMV) infection with upregulation of activating receptor NKG2C. These cells have been shown to possess strong anti-tumour efficacy both in-vitro as well as in-vivo. To determine if reconstitution of adaptive NK cells (CD56 dim NKG2C + NKG2A − ) in patients with advanced leukemia undergoing haploidentical HCT had any impact on disease progression (DP). The study cohort comprised of 60 patients with advanced acute leukemia, aged 2-65 years, receiving myeloablative PTCy based haploidentical transplantation from CMV seropositive donors, followed by CTLA4Ig-primed donor lymphocyte infusions (DLI). They were evaluated for the kinetics of reconstitution of adaptive NK cells, both phenotypic and functional, at days +30,+60, +90 and at regular intervals, to 3 years of follow-up, in relation to DP. Reconstitution of adaptive NK cells was compared with a retrospective cohort of patients in the same protocol receiving DLI without CTLA4Ig. Non-relapse mortality, acute and chronic GVHD were 5.1%, 10.3% and 14.5%. DP was 17.5% at a median follow-up of 28 months. Adaptive NK cells were significantly higher in patients without DP at days+30, +60 and +90 ( p = 0.0001), irrespective of CMV reactivation and remained elevated until 36 months post-HCT. These cells maintained their functional competence as measured by robust interferon-gamma production with higher expressions of KIR, NKG2D and CD57, without any increase in PD1 expression. Grafts from donors with higher adaptive NK cells were associated with a lower risk of DP ( p = 0.0001). In multivariate analysis, adaptive NK cell recovery at day +90 had the most favorable impact on DP (HR-0.7). Tregs reconstituted briskly along with the adaptive NK cells and were sustained as well, without compromising the GVL effect. Comparison with a retrospective cohort receiving the same protocol with DLI without CTLA4Ig, showed a superior reconstitution of adaptive NK cells in those receiving CTLA4Ig-DLI ( p < 0.0001). Our study suggests that myeloablative transplantation from CMV seropositive haploidentical donors augmented with CTLA4Ig-primed DLI might favor early and sustained expansion of functionally competent adaptive NK cells irrespective of CMV reactivation, with a favorable outcome." @default.
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• W3114208348 date "2021-02-01" @default.
• W3114208348 modified "2023-10-01" @default.
• W3114208348 title "Early and Sustained Expansion of Adaptive Natural Killer Cells Following Haploidentical Transplantation and CTLA4Ig-Primed Donor Lymphocyte Infusions Dissociate Graft-versus-Leukemia and Graft-versus-Host Effects" @default.
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• W3114208348 doi "https://doi.org/10.1016/j.jtct.2020.10.005" @default.
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