Research project

A retrospective analysis to evaluate if KIR B haplotype donors confer a reduced risk of relapse in patients with haematological malignancies following haploidentical transplantation at the blood and bone marrow unit at Hammersmith Hospital ICHNHST

Histocompatibility and Immunogenetics
Christopher Byrnes
Training location
Hammersmith Hospital, Imperial College Healthcare NHS Trust

Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells are the first to reconstitute post HPCT, suppressing graft versus host disease and mediating the graft versus leukaemia effect, driven by killer cell immunoglobulin-like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence outcomes of haploidentical HPCT. Haploidentical donors are readily available, and donor selection could hinge on predicted KIR NK cell alloreactivity.

This study investigates whether donors with greater KIR B motifs associate with greater relapse free survival (RFS), overall survival (OS), non-relapse mortality (NRM), acute graft versus host disease (GvHD) and infection. Following KIR genotyping, seventy-seven haploidentical donor recipient pairs (myeloablative n = 30, RIC n = 47) with various haematological malignancies are categorised into neutral (n = 49) or better and best (n = 28), using KIR B motif content. Kaplan-Meier and Cox Regression survival functions are performed to investigate associations with potential outcomes.

Our results show that the better and best category has significantly reduced RFS (p = .004) (HR 4.13, 95% CI 1.45–11.74: p = .008) and trend towards greater infections (p = .080) (HR 2.09, 95% CI 0.90–4.84: p < .1), decreasing OS (p = .008) (HR2.44, 95% confidence interval [CI] 1.24–4.81: p = .01), without impacting GvHD or NRM. In our study, neutral donor outcomes are favourable in T cell depleted haplo-HPCT, potentially due to alloresponsive donor NK cells being targeted by immunosuppressive PTCy treatment delaying reconstitution. Further studies focusing on a homogenous pathology and treatment modality would determine the utility of KIR B content calculator in haploidentical donor selection.

Last updated on 2nd March 2023