EFFECT OF DONOR KIR GENOTYPE ON THE OUTCOME OF PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
(Abstract release date: 05/19/16)
EHA Library. Hoe Koo H. 06/09/16; 133075; E1526
Hong Hoe Koo
Contributions
Contributions
Abstract
Abstract: E1526
Type: Eposter Presentation
Background
Natural Killer (NK) cells have recently attracted for the potential role in graft-versus-tumor effect and NK cell alloreactivity was investigated in several studies.
Aims
The impact of donor killer immunoglobulin-like receptor (KIR) phenotype and genotype on the outcome following allogeneic hematopoietic stem cell transplantation (HSCT) in children was evaluated.
Methods
We prospectively evaluated the gene content and expression of the KIR in children undergoing allogeneic HSCT for malignant diseases. The incompatibility between donor KIR and recipient KIR ligand (receptor-ligand (R-L) mismatch) was defined if the donor has an inhibitory receptor for which the cognate ligand is absent in the recipient. Donors were assigned to A or B KIR haplotype donor according to their gene content. A haplotype donor was defined as the individual having only genes of the group A KIR haplotypes. All other individuals having one or more B haplotype specific genes were defined as B haplotype donor.
Results
All 42 patients received allogeneic HSCT from sibling (n=11), unrelated donor (n=20), or haploidentical donor (n=11) between January 2011 and December 2013. Seventeen transplants were performed in patients with acute myeloid leukemia, 15 in patients with acute lymphoblastic leukemia, 8 in patients with neuroblastoma, and 2 in patients with other solid tumors. Five donor-recipient pairs had KIR R-L match and remaining 37 donor-recipient pairs had KIR R-L mismatch. The 2-year relapse-free survival (RFS) was 100% in recipients with R-L match and 69.3 ± 8.9% in recipients with R-L mismatch, respectively (P=0.18). However, recipients who received HSCT from B haplotype donor had better RFS than those who received HSCT from A haplotype donor (93.3 ± 6.4% vs. 58.0 ± 12.0%, P=0.03). Furthermore, there was no relapse in four recipients who received HSCT from donors having 2 or more B gene-content motifs. Survival benefit of B haplotype donors was found in both HLA-matched and mismatched transplants. Donor KIR genotype and R-L mismatch did not have any significant effect on rates of grade III-IV acute graft-versus-host disease (GVHD) or chronic GVHD. In multivariate analysis, A haplotype was the only independent factor predicting increased risk of relapse (RR 16.5, 95% CI 1.3-217.4, P=0.03).
Conclusion
This analysis has identified decreased relapse and improved RFS in patients who received allogeneic HSCT from donors having B haplotype. KIR genotyping should be considered for successful selection of a NK cell alloreactive donor.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, KIR
Type: Eposter Presentation
Background
Natural Killer (NK) cells have recently attracted for the potential role in graft-versus-tumor effect and NK cell alloreactivity was investigated in several studies.
Aims
The impact of donor killer immunoglobulin-like receptor (KIR) phenotype and genotype on the outcome following allogeneic hematopoietic stem cell transplantation (HSCT) in children was evaluated.
Methods
We prospectively evaluated the gene content and expression of the KIR in children undergoing allogeneic HSCT for malignant diseases. The incompatibility between donor KIR and recipient KIR ligand (receptor-ligand (R-L) mismatch) was defined if the donor has an inhibitory receptor for which the cognate ligand is absent in the recipient. Donors were assigned to A or B KIR haplotype donor according to their gene content. A haplotype donor was defined as the individual having only genes of the group A KIR haplotypes. All other individuals having one or more B haplotype specific genes were defined as B haplotype donor.
Results
All 42 patients received allogeneic HSCT from sibling (n=11), unrelated donor (n=20), or haploidentical donor (n=11) between January 2011 and December 2013. Seventeen transplants were performed in patients with acute myeloid leukemia, 15 in patients with acute lymphoblastic leukemia, 8 in patients with neuroblastoma, and 2 in patients with other solid tumors. Five donor-recipient pairs had KIR R-L match and remaining 37 donor-recipient pairs had KIR R-L mismatch. The 2-year relapse-free survival (RFS) was 100% in recipients with R-L match and 69.3 ± 8.9% in recipients with R-L mismatch, respectively (P=0.18). However, recipients who received HSCT from B haplotype donor had better RFS than those who received HSCT from A haplotype donor (93.3 ± 6.4% vs. 58.0 ± 12.0%, P=0.03). Furthermore, there was no relapse in four recipients who received HSCT from donors having 2 or more B gene-content motifs. Survival benefit of B haplotype donors was found in both HLA-matched and mismatched transplants. Donor KIR genotype and R-L mismatch did not have any significant effect on rates of grade III-IV acute graft-versus-host disease (GVHD) or chronic GVHD. In multivariate analysis, A haplotype was the only independent factor predicting increased risk of relapse (RR 16.5, 95% CI 1.3-217.4, P=0.03).
Conclusion
This analysis has identified decreased relapse and improved RFS in patients who received allogeneic HSCT from donors having B haplotype. KIR genotyping should be considered for successful selection of a NK cell alloreactive donor.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, KIR
Abstract: E1526
Type: Eposter Presentation
Background
Natural Killer (NK) cells have recently attracted for the potential role in graft-versus-tumor effect and NK cell alloreactivity was investigated in several studies.
Aims
The impact of donor killer immunoglobulin-like receptor (KIR) phenotype and genotype on the outcome following allogeneic hematopoietic stem cell transplantation (HSCT) in children was evaluated.
Methods
We prospectively evaluated the gene content and expression of the KIR in children undergoing allogeneic HSCT for malignant diseases. The incompatibility between donor KIR and recipient KIR ligand (receptor-ligand (R-L) mismatch) was defined if the donor has an inhibitory receptor for which the cognate ligand is absent in the recipient. Donors were assigned to A or B KIR haplotype donor according to their gene content. A haplotype donor was defined as the individual having only genes of the group A KIR haplotypes. All other individuals having one or more B haplotype specific genes were defined as B haplotype donor.
Results
All 42 patients received allogeneic HSCT from sibling (n=11), unrelated donor (n=20), or haploidentical donor (n=11) between January 2011 and December 2013. Seventeen transplants were performed in patients with acute myeloid leukemia, 15 in patients with acute lymphoblastic leukemia, 8 in patients with neuroblastoma, and 2 in patients with other solid tumors. Five donor-recipient pairs had KIR R-L match and remaining 37 donor-recipient pairs had KIR R-L mismatch. The 2-year relapse-free survival (RFS) was 100% in recipients with R-L match and 69.3 ± 8.9% in recipients with R-L mismatch, respectively (P=0.18). However, recipients who received HSCT from B haplotype donor had better RFS than those who received HSCT from A haplotype donor (93.3 ± 6.4% vs. 58.0 ± 12.0%, P=0.03). Furthermore, there was no relapse in four recipients who received HSCT from donors having 2 or more B gene-content motifs. Survival benefit of B haplotype donors was found in both HLA-matched and mismatched transplants. Donor KIR genotype and R-L mismatch did not have any significant effect on rates of grade III-IV acute graft-versus-host disease (GVHD) or chronic GVHD. In multivariate analysis, A haplotype was the only independent factor predicting increased risk of relapse (RR 16.5, 95% CI 1.3-217.4, P=0.03).
Conclusion
This analysis has identified decreased relapse and improved RFS in patients who received allogeneic HSCT from donors having B haplotype. KIR genotyping should be considered for successful selection of a NK cell alloreactive donor.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, KIR
Type: Eposter Presentation
Background
Natural Killer (NK) cells have recently attracted for the potential role in graft-versus-tumor effect and NK cell alloreactivity was investigated in several studies.
Aims
The impact of donor killer immunoglobulin-like receptor (KIR) phenotype and genotype on the outcome following allogeneic hematopoietic stem cell transplantation (HSCT) in children was evaluated.
Methods
We prospectively evaluated the gene content and expression of the KIR in children undergoing allogeneic HSCT for malignant diseases. The incompatibility between donor KIR and recipient KIR ligand (receptor-ligand (R-L) mismatch) was defined if the donor has an inhibitory receptor for which the cognate ligand is absent in the recipient. Donors were assigned to A or B KIR haplotype donor according to their gene content. A haplotype donor was defined as the individual having only genes of the group A KIR haplotypes. All other individuals having one or more B haplotype specific genes were defined as B haplotype donor.
Results
All 42 patients received allogeneic HSCT from sibling (n=11), unrelated donor (n=20), or haploidentical donor (n=11) between January 2011 and December 2013. Seventeen transplants were performed in patients with acute myeloid leukemia, 15 in patients with acute lymphoblastic leukemia, 8 in patients with neuroblastoma, and 2 in patients with other solid tumors. Five donor-recipient pairs had KIR R-L match and remaining 37 donor-recipient pairs had KIR R-L mismatch. The 2-year relapse-free survival (RFS) was 100% in recipients with R-L match and 69.3 ± 8.9% in recipients with R-L mismatch, respectively (P=0.18). However, recipients who received HSCT from B haplotype donor had better RFS than those who received HSCT from A haplotype donor (93.3 ± 6.4% vs. 58.0 ± 12.0%, P=0.03). Furthermore, there was no relapse in four recipients who received HSCT from donors having 2 or more B gene-content motifs. Survival benefit of B haplotype donors was found in both HLA-matched and mismatched transplants. Donor KIR genotype and R-L mismatch did not have any significant effect on rates of grade III-IV acute graft-versus-host disease (GVHD) or chronic GVHD. In multivariate analysis, A haplotype was the only independent factor predicting increased risk of relapse (RR 16.5, 95% CI 1.3-217.4, P=0.03).
Conclusion
This analysis has identified decreased relapse and improved RFS in patients who received allogeneic HSCT from donors having B haplotype. KIR genotyping should be considered for successful selection of a NK cell alloreactive donor.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, KIR
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