Decreased iKIR-HLA C Pair Confers Worse Clinical Outcomes for Patients With Myeloid Disease Receiving Antithymocyte Globulin-Based Haploidentical Hematopoietic Stem Cell Transplantation

Front Immunol. 2021 Feb 4:11:614488. doi: 10.3389/fimmu.2020.614488. eCollection 2020.

Abstract

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with malignant hematologic diseases. Killer immunoglobin-like receptor (KIR) expressed by NK cells is closely associated with the transplant outcomes, and it has been widely explored and debated for a few decades. Recently published studies have revealed that inhibitory KIRs (iKIRs) are educated by their cognate human lymphocyte antigen (HLA) ligands, and that decreased iKIR-HLA pairs post-transplantation may indicate a reduced NK cell function and impaired control of the primary disease. However, this theory still needs to be validated by additional clinical studies. Here we conducted a retrospective analysis of 246 patients who received haploidentical (haplo)-HSCT at our treatment center between January 2015 and June 2018. Our data suggests that decreased iKIR-HLA C pair post-HSCT correlated with a significantly higher risk of relapse [hazard risk (HR) = 2.95, p = 0.019] and reduced overall survival (OS) (HR = 3.74, p = 0.001) and disease-free survival (DFS) (HR = 4.05, p = 0.0004) in patients with myeloid disease. In conclusion, decreased iKIR-HLA C pair should be avoided during anti-thymocyte globulin (ATG)-based haplo-HSCT, especially for patients with myeloid disease.

Keywords: KIR; hematopoietic stem cell transplantation; iKIR-HLA model; relapse; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antilymphocyte Serum / immunology*
  • Child
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / immunology
  • Disease-Free Survival
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology
  • Female
  • Graft vs Host Disease / immunology
  • HLA-C Antigens / blood*
  • HLA-C Antigens / immunology
  • Hematologic Neoplasms / immunology*
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematologic Neoplasms / virology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Histocompatibility Testing
  • Humans
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / metabolism*
  • Receptors, KIR / blood*
  • Receptors, KIR / immunology
  • Retrospective Studies

Substances

  • Antilymphocyte Serum
  • HLA-C Antigens
  • Receptors, KIR