PB1741 KIR‐LIGAND MISMATCH IS NOT PREDICTIVE FOR LEUKEMIA‐FREE SURVIVAL IN PATIENTS WITH FAVORABLE RISK AML AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION.
Authors: Van Gelder M. , Billen E. , Voorter C. , Schouten H. , Bos G. , Wieten L. 
Published: June 2019

Background:Evidence suggests that Natural Killer (NK) Cells may play a role in the prevention of relapse of Acute Myeloid Leukemia after allogeneic stem cell transplantation (alloSCT). In a specific condition being HLA mismatched transplants, NK cells may get activated because subsets of donor NK cells miss inhibitory HLA alleles on the patient's cells. This is called. KIR‐ligand mismatch, were subsets of donor NK cells get activated when the patient's HLA alleles are not fitting to one or two of the inhibitory KIRs expressed on the donor cells (Ruggeri, Science 2002). The prerequisite for effective KIR‐ligand mismatch seems to be extensive AGVHD prevention by CD34‐selection of the stem cell graft or intense immunosuppressive conditioning including ATG. In HLA‐matched sibling alloSCT the same beneficial effect of KIR‐ligand mismatch was observed when intense T cell depletion of the graft had been applied (Hsu et al., Blood 2005). It was shown that early post T‐cell depleted alloSCT normally hyporesponsive NK cells expressing KIR for non‐self HLA temporarily displayed full functional capacity (Hsu, Blood 2009).Aims:We hypothesized that a beneficial effect of KIR‐ligand mismatch effect may be present in autologous SCT (autoHCT) in AML, where GVHD obviously is impossible. This would imply that developing NK cells harboring one or two inhibitory KIR receptors (iKIRs) for which no fitting HLA‐allele is present might temporarily get activated in those patients that do not bear all three relevant groups of HLA‐alleles (Bw4, C1 and C2) for which inhibitory KIRs are almost always there (presence of KIR2DL2/3 (fitting C1), KIR2DL1 (fitting C2) and KIR3DL1 (fitting Bw4) is 100%, 92.7% and 92.1% respectively, Hsu, Blood 2005). Approximately 30% of the population bears all three ligands for these three iKIRs and are not susceptible for KIR‐ligand mismatch.Methods:We typed all autologous transplanted AML patients in our center with genetic favorable risk factors (according to ELN 2017) and in first complete remission for HLA Bw4, C1 and C2. 2‐year leukemia‐free survival (LFS) of those patients not susceptible for KIR‐ligand mismatch was compared with LFS of those being susceptible. It was expected that 33% of the auto‐transplanted patients would relapse (Vellenga, Blood 2011). Assuming a meaningful higher 2‐year LFS of 87% for patients missing at least ligand (i.e. 15% higher than observed for the whole population), 2‐year LFS in those not missing a KIR ligand would have been 32% (3x 72 = 216; 216 – (2x 87) = 216 – 174 = 32). To demonstrate this difference 9 patients per group are needed. However, because of the unequal distribution of the two groups (“missing no KIR ligand” vs. “missing at least 1i KIR ligand”) to ensure that the “not missing a KIR ligand group” contains 9 patients at least 3x9=27 patients are needed.Results:We identified 39 favorable risk auto‐transplanted AML patients. Twelve had all HLA ligands for all three iKIRs present, and 27 lacked at least one ligand. 2‐year LFS was 83% and 83% respectively. For those 11 that missed HLA C1 ligands (for which all individuals have a ligand (i.e. KIR2DL2/3) 2‐year LFS was 81%.Summary/Conclusion:2‐year LFS is very high after autoHCT in first complete remission in favorable risk AML and KIR‐ligand mismatch is not relevant.image