ABSTRACT
Matching for HLA class I alleles, including HLA-C, is an important criterion for outcome of unrelated donor
transplantation. However, haplotype-mismatched transplantations for myeloid malignancies, mismatched for
killer immunoglobulin-like receptor (KIR) ligands in the graft-versus-host (GVH) direction, is associated with
lower rates of graft-versus-host disease (GVHD), relapse, and mortality. This study investigated the effect of
KIR ligand mismatching on the outcome of unrelated donor transplantation. The outcomes after 1571
unrelated donor transplantations for myeloid malignancies where donor–recipient pairs were HLA-A, -B, -C,
and -DRB1 matched (n 1004), GVH KIR ligand–mismatched (n 137), host-versus-graft (HVG) KIR
ligand–mismatched (n 170), and HLA-B and/or –C–mismatched but KIR ligand–matched (n 260) were
compared using Cox regression models. Treatment-related mortality (TRM), treatment failure, and overall
mortality were lowest after matched transplantations. Patients who received grafts from donors mismatched at
the KIR ligand in the GVH or HVG direction and mismatched at HLA-B and/or C but matched at the KIR
ligand had similar rates of TRM, treatment failure, and overall mortality. There were no differences in
leukemia recurrence between the 4 groups. These results do not support the choice of an unrelated donor on
the basis of KIR ligand mismatch determined from HLA typing.
ABSTRACTMatching for HLA class I alleles, including HLA-C, is an important criterion for outcome of unrelated donortransplantation. However, haplotype-mismatched transplantations for myeloid malignancies, mismatched forkiller immunoglobulin-like receptor (KIR) ligands in the graft-versus-host (GVH) direction, is associated withlower rates of graft-versus-host disease (GVHD), relapse, and mortality. This study investigated the effect ofKIR ligand mismatching on the outcome of unrelated donor transplantation. The outcomes after 1571unrelated donor transplantations for myeloid malignancies where donor–recipient pairs were HLA-A, -B, -C,and -DRB1 matched (n 1004), GVH KIR ligand–mismatched (n 137), host-versus-graft (HVG) KIRligand–mismatched (n 170), and HLA-B and/or –C–mismatched but KIR ligand–matched (n 260) werecompared using Cox regression models. Treatment-related mortality (TRM), treatment failure, and overallmortality were lowest after matched transplantations. Patients who received grafts from donors mismatched atthe KIR ligand in the GVH or HVG direction and mismatched at HLA-B and/or C but matched at the KIRligand had similar rates of TRM, treatment failure, and overall mortality. There were no differences inleukemia recurrence between the 4 groups. These results do not support the choice of an unrelated donor onthe basis of KIR ligand mismatch determined from HLA typing.
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