Donor KIR2DS1-mediated Decreased Relapse and Improved Survival, Depending on Remission Status at HLA-Haploidentical Transplantation with Post-transplantation Cyclophosphamide.

HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without HLA-matched related or unrelated donors. PT/Cy-haplo could provide more patients the opportunity to receive allo-HCT, since most patients have more than one available HLA-haploidentical related donor candidate. In PT/Cy-haplo settings, however, an optimal donor selection algorithm has not yet been established. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who received PT/Cy-haplo at our institute. In both patients and donors, HLA allele genotyping was performed for HLA-A, -B, -C, and -DRB1 and 16 KIR genes were genotyped. Patients in complete remission (CR) who underwent PT/Cy-haplo from KIR2DS1-positive donors had significantly lower rates of cumulative incidence of relapse (CIR) than those who underwent PT/Cy-haplo from KIR2DS1-negative donors (1-year CIR, 0.0% vs. 32.6%, P = 0.037; 2-year CIR, 9.2% vs. 42%, P = 0.037). Moreover, PT/Cy-haplo from KIR2DS1-positive donors was significantly associated with improved overall survival (OS) (1-year OS, 91.7% vs. 58.7%, P = 0.010; 2-year OS, 83% vs. 34%, P = 0.010). In contrast, in non-CR individuals, PT/Cy-haplo from KIR2DS1-positive donors did not significantly improve CIR or OS (1-year CIR 56.5% vs. 64.7%, P = 0.973; 2-year CIR, not reached vs. 64.7%, not evaluable; 1-year OS, 25.4% vs. 20.6%, P = 0.418; 2-year OS, 5.1% vs. 20.6%, P = 0.418). Additionally, lower infused CD34+ cell dose, female-to-male transplantation, and acute myeloid leukemia were significantly associated with increased risk of relapse and mortality. In conclusion, the present study demonstrated that graft-versus-leukemia/tumor effects were exerted through donor KIR2DS1 at PT/Cy-haplo when patients have low tumor burdens. It would be worth examining the inclusion of donor KIR genotyping and disease status assessment in establishing optimal donor selection criteria at PT/Cy-haplo.