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

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.

Effect of donor characteristics on T cell‐replete haploidentical stem cell transplantation over the last 10 years at a single institution

“…Cytomegalovirus (CMV) serological state was not considered a covariate because of the high prevalence of CMV infection in Chinese people. Killer immunoglobulin‐like receptor matching was not analysed because of too little data and having been reported previously 34 …”

“…Killer immunoglobulin-like receptor matching was not analysed because of too little data and having been reported previously. 34…”

NK cell education: Physiological and pathological influences

“…However, relapse remains the main cause of mortality after HSCT (99). Effector educated NK cells from a donor (D n ) play a key role in immune response reactivity and in the risk of relapse following HSCT (57,(100)(101)(102). Indeed, the educated NK cells must be calibrated by self-HLA-I molecules from a receiver (R r ) to preserve immune tolerance after transplantation and reconstitute the effector NK cell response to conserve leukemia control.…”

Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

“…Ongoing studies focusing on relapse, infections, and hematopoietic and immunological reconstitution enhancement would further improve haploidentical transplant outcomes of AML. In the long term, biomarkers (163,164), such as MRD, directed donor selection (108), conditioning selection (14), and immunological enhancement for relapse intervention (165), will help us realize precision medicine in the setting of haplo-SCT for treating patients with AML.…”