What is the most likely increased risk with KIR (Killer-cell Immunoglobulin Receptor) B ligand mismatching in a donor?

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Last updated: March 25, 2025 • View editorial policy

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From the Guidelines

KIR B ligand mismatching in a donor is most likely to increase the risk of graft-versus-host disease (GVHD) rather than reducing it, but the primary concern with KIR B ligand matching is the increased risk of relapse in patients with hematologic malignancies after hematopoietic stem cell transplantation. When a donor's killer immunoglobulin-like receptor (KIR) B haplotype matches with the recipient's human leukocyte antigen (HLA) ligands, it can lead to reduced graft-versus-leukemia (GVL) effect, as the natural killer (NK) cells from the donor become tolerant to the recipient's cells, reducing their ability to recognize and eliminate residual malignant cells 1. The KIR-HLA interaction is crucial for NK cell education and function, and when there is matching rather than mismatching, the beneficial alloreactivity of donor NK cells against recipient leukemia cells is diminished.

Key Considerations

  • The GVL effect contributes significantly to treatment success in transplants for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and other hematologic malignancies.
  • Clinicians should consider KIR-ligand mismatching when selecting optimal donors to enhance anti-tumor immunity post-transplantation.
  • The selection of an optimal haploidentical donor (HID) involves considering factors such as the donor's age, sex, and relationship to the recipient, as well as the presence of donor-specific anti-HLA antibodies (DSAs) and the KIR-ligand mismatch status.

Donor Selection

  • Younger donors and male donors are associated with lower non-relapse mortality (NRM) and higher overall survival (OS) rates 1.
  • Father donors are associated with lower NRM and acute GVHD (aGVHD) rates, as well as higher OS rates, compared to mother donors.
  • The order of rank for haplo donor characteristics is young, male, and non-inherited maternal antigen mismatch.
  • Transplants from older mothers and NIPA-mismatched donors should be avoided as much as possible.

KIR-Ligand Mismatching

  • KIR B ligand mismatching can enhance the GVL effect and reduce the risk of relapse in patients with hematologic malignancies.
  • The KIR-ligand mismatch status should be considered when selecting an optimal HID to enhance anti-tumor immunity post-transplantation.

From the Research

Increased Risk with KIR B Ligand Mismatching

  • The most likely increased risk with KIR B ligand mismatching in a donor is chronic graft-versus-host disease (cGVHD) 2.
  • KIR genotype mismatching, such as KIR-B/x donor into KIR-AA recipient or vice versa, is associated with a significant increase in cGVHD 2.
  • The incidence of cGVHD is higher in recipients who have one or two C1 bearing HLA-C epitopes (HLA-C1/x) when receiving grafts from KIR genotype mismatched donors 2.
  • Activating KIR incompatibilities, where the recipient is negative and the donor is positive, can also enhance GVHD and affect survival after allogeneic hematopoietic stem cell transplantation 3.
  • Donor-recipient KIR-ligand incompatibility can have varying effects on outcomes, ranging from beneficial to detrimental, depending on the methodology, disease distribution, and transplant protocol or donor type 4.

KIR Genotype Matching and Outcomes

  • Donor-recipient KIR genotype matching has a protective effect on chronic GVHD and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation 5.
  • Matching for activating KIR (aKIR) can decrease relapse rate and increase disease-free survival, while matching for inhibitory KIR (iKIR) can reduce the incidence of cGVHD 5.
  • The presence of particular activating KIRs in the donor, with their absence in the recipient, can enhance GVHD without a beneficial graft-versus-leukemia effect 3.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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