Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Ido, Kentaro; Koh, Hideo; Hirose, Asao; Seto, Toshiyuki; Makuuchi, Yosuke; Kuno, Masatomo; Takakuwa, Teruhito; Okamura, Hiroshi; Nanno, Satoru; Nakamae, Mika; Nishimoto, Mitsutaka; Nakashima, Yasuhiro; Hino, Masayuki; Nakamae, Hirohisa

doi:10.1016/j.jtct.2021.09.019

Cited by 4 publications

(5 citation statements)

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“…Omitting four DNA samples with missing data, the NKG2D genotype (3 0 UTR 5 0 -3 0 ) frequencies of LNK1/LNK1 (G/G), LNK1/HNK1 (G/C) and HNK1/HNK1 (C/C) were 53%, 37%, and 10%, respectively, and in agreement with Hardy-Weinberg equilibrium goodness of fit ( p = .237). These frequencies vary slightly from published studies in Japanese populations 17,19,20 as the overall allele frequency of HNK1 (28%) is lower and LNK1 (72%) is higher in our population, indicating genetic variation based on ethnicity.…”

Section: Frequencies Of Nkg2d and Mica-129 Genotypes And Allelescontrasting

confidence: 84%

“…Ido et al 20 investigated 91 HLA‐haploidentical recipients receiving post‐transplant cyclophosphamide with or without ATG and showed that amongst ATG‐recipients, relapse was lower when grafts were LNK1 homozygous. They then stratified AML and non‐AML patients, revealing that non‐AML ATG‐recipients receiving LNK1 homozygous grafts had increased OS and decreased relapse.…”

Section: Discussionmentioning

confidence: 99%

“…18 To date, only three studies have investigated LNK1/HNK1 SNPs and HCT outcomes such as acute and chronic GVHD (aGVHD, cGVHD), relapse, and overall survival (OS), with differing or conflicting results. [19][20][21] We investigated the MICA-129 met/val and NKG2D LNK1/ HNK1 genotypes of 267 cord blood units (CBU) used for 178 adult and 87 paediatric HCTs for malignant diseases. We hypothesised higher NKG2D expression due to the HNK1 SNP would increase functional potency of donor-derived NK cells and decrease relapse by targeting residual leukemic cells or reduce GVHD by killing host antigen-presenting dendritic cells and alloreactive GVHD-inducing T cells.…”

Section: Introductionmentioning

confidence: 99%

“…The authors also found that miR‐1245 expression was upregulated by TGF‐β1 released by tumour cells 18 . To date, only three studies have investigated LNK1/HNK1 SNPs and HCT outcomes such as acute and chronic GVHD (aGVHD, cGVHD), relapse, and overall survival (OS), with differing or conflicting results 19–21 …”

Section: Introductionmentioning

confidence: 99%

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Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases

Cox,

Patterson,

Duggleby

et al. 2024

European J of Haematology

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ObjectivesNKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome.MethodsWe retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes.ResultsIn adult patients, LNK1 homozygous CB significantly improved 60‐day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4–0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60‐day engraftment (HR 0.4; 95% CI 0.2–0.7; p = .003), as did MICA‐129 methionine+ CB grafts (HR 1.7 95% CI 1.1–2.6; p = .02).ConclusionCB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

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Section: Frequencies Of Nkg2d and Mica-129 Genotypes And Allelescontrasting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases

Cox,

Patterson,

Duggleby

et al. 2024

European J of Haematology

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“…In our study, PTCy-haplo from donors with NKG2D rs1049174 CC was associated with a significantly decreased risk of relapse/progression (adjusted HR, 0.2, P=.007) when compared those with NKG2D rs1049174 GG. A positive effect of the rs1049174 CC donor on relapse/progression was noted in patients with diseases other than AML ( 84 ).…”

Section: The Effect Of Alloreactivity Of Nk Cells On the Gvt Effect I...mentioning

confidence: 99%

Graft-versus-tumor effect of post-transplant cyclophosphamide-based allogeneic hematopoietic cell transplantation

Nakamae

2024

Front. Immunol.

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Post-transplant cyclophosphamide (PTCy) is becoming the standard prophylaxis for graft-versus-host disease (GVHD) in HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) and in HLA-matched allo-HCT. Immune reconstitution in the post-transplant setting may influence the graft-versus-tumor (GVT) effect because PTCy has a profound effect on T cell and natural killer cell functions and their reconstitution after allo-HCT. However, many recent studies have shown that the incidence of relapse after allo-HCT with PTCy is comparable to that after conventional allo-HCT. To further improve the outcomes, it is critical to establish a strategy to maintain or effectively induce the GVT effect when using PTCy as a platform for GVHD prophylaxis. However, there is a paucity of studies focusing on the GVT effect in allo-HCT with PTCy. Therefore, focusing on this issue may lead to the establishment of more appropriate strategies to improve transplantation outcomes without exacerbating GVHD, including novel therapies involving cell modification.

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Donor NKG2D rs1049174 polymorphism predicts hematopoietic recovery and event-free survival after single-unit cord blood transplantation in adults

Konuma,

Hamatani-Asakura,

Monna-Oiwa

et al. 2024

Bone Marrow Transplant

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Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Cited by 4 publications

References 44 publications

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases

Graft-versus-tumor effect of post-transplant cyclophosphamide-based allogeneic hematopoietic cell transplantation

Donor NKG2D rs1049174 polymorphism predicts hematopoietic recovery and event-free survival after single-unit cord blood transplantation in adults

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