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The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transplantations for hematologic malignancies. In addition to KIR ligand status, we considered the donors' activating KIRs and grafted NK, T, and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005) and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n = 47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P = .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2 heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P = .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03). Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT, but argue against a favorable impact of missing KIR ligands in the given setting. We conclude that the mechanism favoring the missing KIR ligand constellation in T cell depleted BMT may not operate in T cell replete PBSCT. The reasons for this differential effect remain unresolved., (Copyright 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation is frequently complicated by syndromes characterized by a disruption of the endothelial integrity such as graft-versus-host disease or liver toxicity. Vascular endothelial growth factor and activin-A, a member of the transforming growth factor beta (TGF-beta) superfamily, are important for endothelial integrity and tissue repair. We retrospectively measured endogenous vascular endothelial growth factor and activin-A serum levels in 70 patients following allogeneic stem cell transplantation. Vascular endothelial growth factor serum levels were significantly decreased within the first 2 weeks after the transplant and returned to pre transplant levels by day +15. Activin-A serum levels were significantly elevated from day +7 with peak levels reached on day +10. By using the median value as cutoff high vascular endothelial growth factor levels on day +15 were associated with significantly better overall survival, less liver toxicity, faster neutrophil recovery, and a trend towards less severe acute graft-versus-host disease. No correlation was found between activin-A serum levels and survival, liver toxicity, neutrophil recovery, or graft-versus-host disease. Monitoring of vascular endothelial growth factor levels following allogeneic hematopoietic stem cell transplantation might help to identify patients with a very high risk for early transplant-related complications.