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MISMATCHED INHIBITORY KIR LIGANDS PREDICT WORSE OVERALL SURVIVAL IN T-REPLETE HEMATOPOIETIC STEM CELL TRANSPLANTS (HSCTs).
J.Y. Sun MD 1, L. Gaidulis MS 1, A. Dagis 2, J. Palmer PhD 2, R. Rodriguez MD 1, M.M. Miller PhD 3, S.J. Forman MD 1 and D. Senitzer PhD 1. 1 Division of Hematology and Hematopoietic Cell Transplantation (HCT), City of Hope National Medical Center ; 2 Divison of Information Sciences and 3 Division of Molecular Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA .
Natural killer (NK) cells are an important component of the peripheral immune system. Killer Ig-like receptor (KIR) is a major cluster of the NK cell receptors and plays either inhibitory or activating roles. Some inhibitory KIRs recognize HLA-B or Cw epitopes on target cells to regulate NK cell activity. Diversified results came from studies on the effect of alloreactive NK cells in HSCTs. The present study evaluated 273 AML/MDS patients transplanted with T-cell replete hematopoietic stem cells from related or unrelated donors. The KIR genes of patients and donors were retrospectively typed by a multiplex PCR-SSP method. Analysis of KIR genotype with HLA genotype divided the cohort into three groups: 221 HLA compatible cases (A, B, Cw, DRB1, and DQB1 at the *antigen level), 27 HLA incompatible cases, and 25 HLA incompatible plus inhibitory KIR ligand mismatched cases. A very significantly different rate (P=0.002) of overall survival longer than one year was found between the HLA compatible group (126/221, 57%), the HLA incompatible group (10/27, 37%), and the KIR ligand mismatched group (6/25, 24%). Analyses of other clinical endpoints are in progress. The finding contrasts to the beneficial role of mismatched KIR ligands in T-depleted HSCTs, but is consistent with other studies.