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.


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).


CONCLUSIONS
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.
Giebel
S
S
Department of Hematology and BMT, Silesian Medical University, ul. Reymonta 8, 40-029 Katowice, Poland. sgiebel@poczta.onet.pl
Nowak
I
I
Wojnar
J
J
Markiewicz
M
M
Dziaczkowska
J
J
Wylezol
I
I
Krawczyk-Kulis
M
M
Bloch
R
R
Kusnierczyk
P
P
Holowiecki
J
J
D000293:Adolescent; D000328:Adult; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology*; D054340:Receptors, KIR; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors / Q000706:statistics & numerical data; D016896:Treatment Outcome
C496212:KIR2DS1 protein, human; C433932:KIR2DS2 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR