title: Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors.
abstract: The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.
authors.affiliation: Clinical Transplantation Immunology Laboratory, Department of Pathology, Duke University Medical Center (DUMC), Durham, NC 27710, USA.
authors.forename: D-F
authors.initials: DF
authors.lastname: Chen
authors.forename: V K
authors.initials: VK
authors.lastname: Prasad
authors.forename: G
authors.initials: G
authors.lastname: Broadwater
authors.forename: N L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: A
authors.initials: A
authors.lastname: DeOliveira
authors.forename: A
authors.initials: A
authors.lastname: Clark
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: J P
authors.initials: JP
authors.lastname: Chute
authors.forename: M E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: C
authors.initials: C
authors.lastname: Gasparetto
authors.forename: G D
authors.initials: GD
authors.lastname: Long
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: N J
authors.initials: NJ
authors.lastname: Chao
authors.forename: D A
authors.initials: DA
authors.lastname: Rizzieri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D054340:Receptors, KIR / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR