A retrospective analysis to evaluate if KIR B haplotype donors associate with a reduced risk of relapse in patients with haematological malignancies following haploidentical transplantation at the Blood and Bone Marrow Transplant Unit at Hammersmith Hospital ICHNHST

Abstract

Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells suppress graft versus host disease and mediate the graft versus leukaemia effect, driven by killer cell immunoglobulin-like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence graft outcome in haploidentical transplants with varying impacts between patient cohorts. This study investigates whether donors with greater KIR B motifs associate with outcomes such as greater relapse-free survival (RFS), overall survival (OS), nonrelapse mortality (NRM), acute graft versus host disease (GvHD) and infection. The study cohort included 98 haploidentical donor-recipient (D/R) pairs (myeloablative n = 37, RIC n = 61) with various haematological malignancies, receiving primary T-cell replete haploidentical HSCT with PTCγ. Following KIR SSO genotyping, donors are categorised into neutral (n = 63) or better and best (n = 35), based on KIR B motif content. Kaplan-Meier and Cox regression survival functions are performed to investigate associations with outcomes. Our results show that the better and best category has significantly poorer RFS (p = 0.013; hazard ratio [HR] 3.16, 95% CI 1.21-8.24: p = 0.018). The greater risk of relapse associated with poorer OS (p = 0.011; HR 2.24, 95% CI 1.18-4.24: p = 0.01) in the better and best category. The competing KIR receptor-ligand and missing licensing proof models failed to predict transplant outcomes. Here, we show neutral donors associate with favourable outcomes in T-cell replete haplo-HPCT with PTCγ after categorisation using the KIR B content model, due to the increased risk of relapse associated with the use of better and best donors.

Keywords: HLA; haematopoietic progenitor cell transplant; haploidentical transplant; killer cell immunoglobulin-like receptors; natural killer cells.