Beelen Dietrich W, Ottinger Hellmut D, Ferencik Stanislav, Elmaagacli Ahmet H, Peceny Rudolf, Trenschel Rudolf, Grosse-Wilde Hans
Department of Bone Marrow Transplantation, Institute of Immunology, University Hospital of Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Blood. 2005 Mar 15;105(6):2594-600. doi: 10.1182/blood-2004-04-1441. Epub 2004 Nov 9.
It remains controversial whether alloreactive donor-derived natural killer (NK) cells display graft-versus-leukemia reactions after unmodified allogeneic hematopoietic stem cell transplantation (HSCT). The present study evaluated the role of inhibitory killer immunoglobulin-like receptor (KIR) ligand incompatibility using a well-defined and uniform setting of unmodified allogeneic HSCT in 374 patients with myeloid leukemias. The most striking finding was a significant heterogeneity in the 5-year estimates of hematologic leukemic relapse after human leukocyte antigen (HLA)-identical (n = 237; 22%), HLA class I-disparate (n = 89; 18%), and KIR ligand-incompatible transplantations (n = 48; 5%) (P < .04). Multivariate analysis confirmed that the relative relapse risk (RR) was influenced by HLA class I disparity alone (RR 0.49), but was lowest after HLA class I-disparate, KIR ligand-incompatible transplantations (RR 0.24) (P < .008). The primary graft failure rates, however, increased from 0.4% after HLA class I-identical to 2.3% after HLA class I-disparate, and to 6.3% after KIR ligand-incompatible transplantations, respectively (P < .02). Unlike some other reports, no beneficial effect of KIR ligand incompatibility on other major endpoints of allogeneic HSCT (transplantation-related mortality, and overall and event-free survival) was detectable in the present study. In conclusion, unmodified allogeneic HSCT from KIR ligand-incompatible donors provides a superior long-term antileukemic efficacy in patients with myeloid malignancies.
在未修饰的异基因造血干细胞移植（HSCT）后，同种异体反应性供体来源的自然杀伤（NK）细胞是否会表现出移植物抗白血病反应仍存在争议。本研究在374例髓系白血病患者中，使用定义明确且统一的未修饰异基因HSCT方案，评估了抑制性杀伤细胞免疫球蛋白样受体（KIR）配体不相容性的作用。最显著的发现是，在人类白细胞抗原（HLA）相同（n = 237；22%）、HLA I类不相合（n = 89；18%）以及KIR配体不相容移植（n = 48；5%）后的5年血液学白血病复发估计中存在显著异质性（P <.04）。多变量分析证实，相对复发风险（RR）仅受HLA I类不相合影响（RR 0.49），但在HLA I类不相合、KIR配体不相容移植后最低（RR 0.24）（P <.008）。然而，原发性移植物失败率分别从HLA I类相同时的0.4%增加到HLA I类不相合时的2.3%，以及KIR配体不相容移植后的6.3%（P <.02）。与其他一些报告不同，本研究未检测到KIR配体不相容性对异基因HSCT的其他主要终点（移植相关死亡率、总生存率和无事件生存率）有有益影响。总之，来自KIR配体不相容供体的未修饰异基因HSCT为髓系恶性肿瘤患者提供了卓越的长期抗白血病疗效。
