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Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma

  作者 Gabriel, IH; Sergeant, R; Szydlo, R; Apperley, JF; deLavallade, H; Alsuliman, A; Khoder, A; Marin, D; Kanfer, E; Cooper, N; Davis, J; MacDonald, D; Bua, M; Foroni, L; Giles, C; Milojkovic, D; Rahemtulla, A; Rezvani, K  
  选自 期刊  Blood;  卷期  2010年116-12;  页码  2033-2039  
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[摘要]Natural killer (NK) cells exert anti-myeloma 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% Cl, 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. (Blood. 2010;116(12):2033-2039)

 
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