KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia

Abstract

Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS.

Figure 1

(a) Estimated leukemia-free survival in patients with Kir-ligand-compatible (^_______) (n=149) or -incompatible (- - - - - - -) donors (n=69), after UCBT for acute leukemia in CR. (b) Estimated overall survival in patients with Kir-ligand-compatible (^_______) (n=149) or -incompatible (- - - - - - -) donors (n=69), after UCBT for acute leukemia in CR. (c) Cumulative incidence of relapse in patients with Kir-ligand-compatible (^______) (n=149) or -incompatible (- - - - - - - -) donors (n=69), after UCBT for acute leukemia in CR. CR, complete remission; UCBT, unrelated cord blood transplant.

Figure 2

(a) Estimated leukemia-free survival in AML patients in CR with Kir-ligand-compatible (^_______) (n=68) or -incompatible (- - - - - - -) donors (n=26), after UCBT. (b) Estimated leukemia-free survival in ALL patients in CR with Kir-ligand-compatible (^_______) (n=81) or -incompatible (- - - - - - -) donors (n=43), after UCBT. AML, acute myeloid leukemia; CR, complete remission; UCBT, unrelated cord blood transplant.