Effect of missing killer-immunoglobulin-like receptor ligand in recipients undergoing HLA full matched, non-T-depleted sibling donor transplantation: a single institution experience of 151 Asian patients

被引:10
作者
Linn, Y. C. [1 ]
Phang, C. Y. [2 ]
Lim, T. J. [2 ]
Chong, S. F. [3 ]
Heng, K. K. [1 ]
Lee, J. J. [1 ]
Loh, Y. [1 ]
Hwang, W. [1 ]
Goh, Y. T. [1 ]
Koh, M. [1 ,2 ]
机构
[1] Singapore Gen Hosp, Dept Haematol, Singapore 169608, Singapore
[2] Hlth Sci Author, Blood Serv Grp, Singapore, Singapore
[3] Singapore Gen Hosp, Dept Clin Res, Singapore 169608, Singapore
关键词
NK alloreactivity; KIR-ligand; missing ligand model; HLA full-matched sibling transplant; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; HEMATOPOIETIC TRANSPLANTS; MYELOID-LEUKEMIA; UNRELATED DONORS; INHIBITORY KIR; NK CELLS; INCOMPATIBILITY; GRAFT;
D O I
10.1038/bmt.2009.303
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
This retrospective analysis studied the impact of natural killer (NK) alloreactivity based on the missing ligand model, for a cohort of recipients undergoing haemopoietic stem cell transplant without T-cell depletion from HLA full-matched sibling donors. All patients received a uniform myeloablative conditioning regimen and prophylaxis for GVHD. A total of 151 patients were studied, including 62 patients with AML or myelodysplastic syndrome, 42 patients with ALL and 47 patients with CML. We found that 81% of patients had at least one missing KIR-ligand (KIR-L), and HLA-C1 allogroup homozygosity is present in 70% of patients. From multivariate analysis, we observed that the only consistently significant factor that was associated with superior survival was disease stage. Missing KIR-L, whether considering HLA-Bw and HLA-C alleles, without or with HLA-A ligands or narrowing to only HLA-C alleles alone to classify the number of missing KIR-L, did not have any impact on OS or relapse-free survival. This negative finding implies that as the KIR-L composition of recipient is not important in this matched non-T-depleted setting, further immunotherapeutic measures involving adoptive NK cell infusions have to be explored to exploit the benefit of NK alloreactivity for such transplants. Bone Marrow Transplantation (2010) 45, 1031-1037; doi:10.1038/bmt.2009.303; published online 9 November 2009
引用
收藏
页码:1031 / 1037
页数:7
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