title: Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma.
abstract: Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1(+) (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1(+) compared with KIR3DS1(-) was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1(+) in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1(+) KIR3DL1(+) HLA-Bw4(-) had a significantly shorter PFS than patients who were KIR3DS1(-), translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR-human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.
authors.affiliation: Department of Hematology, Imperial College, London, UK.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gabriel
authors.forename: Ruhena
authors.initials: R
authors.lastname: Sergeant
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Hugues
authors.initials: H
authors.lastname: DeLavallade
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alsuliman
authors.forename: Ahmad
authors.initials: A
authors.lastname: Khoder
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.forename: Edward
authors.initials: E
authors.lastname: Kanfer
authors.forename: Nichola
authors.initials: N
authors.lastname: Cooper
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Donald
authors.initials: D
authors.lastname: MacDonald
authors.forename: Marco
authors.initials: M
authors.lastname: Bua
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
authors.forename: Chrissy
authors.initials: C
authors.lastname: Giles
authors.forename: Dragana
authors.initials: D
authors.lastname: Milojkovic
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D015235:HLA-B Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007125:Immunogenetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D054349:Receptors, KIR3DS1 / Q000032:analysis* / Q000235:genetics; D033581:Stem Cell Transplantation / Q000401:mortality*; D014182:Transplantation, Autologous
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D054349:Receptors, KIR3DS1