Giebel Sebastian, Locatelli Franco, Lamparelli Teresa, Velardi Andrea, Davies Stella, Frumento Guido, Maccario Rita, Bonetti Federico, Wojnar Jerzy, Martinetti Miryam, Frassoni Francesco, Giorgiani Giovanna, Bacigalupo Andrea, Holowiecki Jerzy
Department of Haematology and Bone Marrow Transplantation, Silesian Medical Academy, Katowice, Poland.
Blood. 2003 Aug 1;102(3):814-9. doi: 10.1182/blood-2003-01-0091. Epub 2003 Apr 10.
Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was demonstrated to be associated with improved outcome in patients given haploidentical, T-cell-depleted hematopoietic stem cell transplants (HSCTs). The goal of this study was to evaluate whether that observation could be generalized for patients receiving unmanipulated HSCTs from unrelated donors (URD). One hundred thirty patients with hematologic malignancies entered the study. Graft-versus-host disease (GVHD) prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate, and pretransplantation antithymocyte globulin (ATG). Patients were divided into those with (n = 20) and those without (n = 110) KIR ligand incompatibility with respect to their donors. At 4.5 years patients with KIR ligand incompatibility had higher probability of overall survival (87% versus 48%, P =.006) and disease-free survival (87% versus 39%, P =.0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the 2 groups equaled 6% and 40% (P =.01), respectively. Relapse rates for patients receiving transplants from a donor with or without KIR ligand incompatibility were 6% and 21%, respectively (P =.07). All patients with myeloid malignancies receiving transplants from KIR ligand-disparate donors (n = 13) are alive and disease free. These data indicate that natural killer (NK) cell alloreactivity is associated with better outcome after URD-HSC transplantation when ATG is used as part of GVHD prophylaxis.
在单倍体相合、去除T细胞的造血干细胞移植（HSCT）患者中，移植物抗宿主方向的杀伤细胞免疫球蛋白样受体（KIR）配体不相容性被证明与较好的预后相关。本研究的目的是评估这一观察结果是否能推广至接受非亲缘供者（URD）未处理HSCT的患者。130例血液系统恶性肿瘤患者进入该研究。移植物抗宿主病（GVHD）预防措施统一，包括环孢素、短期甲氨蝶呤和移植前抗胸腺细胞球蛋白（ATG）。根据供者情况，患者被分为KIR配体不相容组（n = 20）和KIR配体相容组（n = 110）。在4.5年时，与KIR配体相容患者相比，KIR配体不相容患者的总生存率（87%对48%，P = 0.006）和无病生存率（87%对39%，P = 0.0007）更高。两组的移植相关死亡率分别为6%和40%（P = 0.01）。接受KIR配体不相容或相容供者移植患者的复发率分别为6%和21%（P = 0.07）。所有接受KIR配体不相合供者移植的髓系恶性肿瘤患者（n = 13）均存活且无病。这些数据表明，当将ATG用作GVHD预防措施的一部分时，自然杀伤（NK）细胞同种异体反应性与URD-HSC移植后更好的预后相关。
