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Giebel, S. et al.

Giebel, Nowak, Wojnar, Markiewicz, Dziaczkowska, Wylezol, Krawczyk-Kulis, Bloch, Kusnierczyk, Holowiecki,

Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation.

BACKGROUND: In a previous study we demonstrated that incompatibility regarding ligands for inhibitory killer immunoglobulin-like receptors (KIRs) is associated with a survival advantage following unrelated donor-hematopoietic cell transplantation (URD-HCT). The goal of the present analysis was to evaluate whether genotype of activating KIRs of the donor may have an impact on the outcome of URD-HCT. PATIENTS AND METHODS: Twenty-five URD-HCT recipients with hematological malignancies, mean age 27 years (range, 14-43 years), were included in the analysis. The conditioning regimen was myeloablative and based on chemotherapy alone (n = 20) or total body irradiation (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine, methotrexate, and pretransplant antithymocyte globulin. Patients were grouped according to their donors' activating KIR genotype including two loci: KIR2DS1 and KIR2DS2. RESULTS: The presence of KIR2DS1 in the donor (n = 16/25) was not demonstrated to influence outcome. In contrast, the presence of KIR2DS2 (n = 13/25 donors) was associated with decreased probability of overall survival (0% vs 92%, P = .04) and disease-free survival (0% vs 92%, P = .046). The reason for failures in the KIR2DS2-positive group was chronic GVHD (n = 4), acute GVHD (n = 2), and relapse (n = 1). The cumulative incidence of nonrelapse mortality equaled 90% for the KIR2DS2-positive group and 8% for the KIR2DS2-negative group (P = .09). CONCLUSION: The presence of KIR2DS2 gene in the donor is associated with a high risk of mortality following URD-HCT, resulting mainly from the incidence of severe GVHD. Whether this effect is associated with the activity of natural killer cells or KIR-bearing T lymphocytes requires further investigation.[1]

References

Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation. Giebel, S., Nowak, I., Wojnar, J., Markiewicz, M., Dziaczkowska, J., Wylezol, I., Krawczyk-Kulis, M., Bloch, R., Kusnierczyk, P., Holowiecki, J. Transplant. Proc. (2006) [Pubmed]

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