Increased donor inhibitory KIR are associated with reduced GVHD and improved survival following HLA-matched unrelated donor HCT in paediatric acute leukaemia.
Elizabeth KriegerRehan QayyumAmir Ahmed ToorPublished in: British journal of haematology (2024)
Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes.
Keyphrases
- nk cells
- end stage renal disease
- clinical trial
- free survival
- stem cell transplantation
- liver failure
- intensive care unit
- newly diagnosed
- chronic kidney disease
- ejection fraction
- emergency department
- high dose
- respiratory failure
- low dose
- type diabetes
- drug induced
- gene expression
- metabolic syndrome
- risk assessment
- patient reported outcomes
- acute myeloid leukemia
- cell proliferation
- transcription factor
- blood pressure
- aortic dissection
- patient reported
- cord blood
- heart rate
- machine learning
- signaling pathway
- insulin resistance
- high intensity
- cell cycle arrest