Sun Joel Y, Dagis Andrew, Gaidulis Laima, Miller Marcia M, Rodriguez Roberto, Parker Pablo, Nademanee Auayporn, Falk Peter, Rosenthal Joseph, Forman Stephen J, Senitzer David
Division of Hematology and HCT, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA.
Biol Blood Marrow Transplant. 2007 Feb;13(2):197-205. doi: 10.1016/j.bbmt.2006.09.009.
In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n = 101), acute myeloid leukemia and myelodysplastic syndrome (n = 149), and chronic myeloid leukemia (n = 128). The cohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n = 260); in group 2, HLA class I mismatched at the antigen level (n = 57); and in group 3, HLA class I and iKIRLs mismatched (n = 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P = .002). In contrast to group 2, group 3 had statistically lower OS (P = .05) and event-free survival (P = .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n = 246, P = .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.
在造血细胞移植（HCT）中，杀伤细胞免疫球蛋白样受体（iKIRL）的抑制性配体赋予的自然杀伤细胞同种异体反应性可能会产生有益或有害的结果。更多数据可能有助于解决这个复杂问题。我们分析了378例急性淋巴细胞白血病（n = 101）、急性髓细胞白血病和骨髓增生异常综合征（n = 149）以及慢性髓细胞白血病（n = 128）的T细胞充足移植物的原发性同种异体移植。该队列分为3组：第1组，HLA I类抗原水平匹配（n = 260）；第2组，HLA I类抗原水平不匹配（n = 57）；第3组，HLA I类和iKIRL不匹配（n = 61）。第1组（59%）、第2组（49%）和第3组（30%）的1年总生存率（OS）有显著差异（P = 0.002）。与第2组相比，第3组的OS在统计学上较低（P = 0.05），无事件生存率也较低（P = 0.01）。复发和无复发生存期死亡率似乎导致了第3组的低OS。当对缺乏iKIRL的患者进行HLA匹配移植分析时，自然杀伤细胞同种异体反应性的有害影响也很明显。缺乏HLA-Cw第1或2组iKIRL的患者的1年OS显著低于有iKIRL的患者（55%对67%，n = 246，P = 0.01）。我们的观察结果表明，在T细胞充足的非亲缘HCT中，iKIRL不匹配和缺乏iKIRL会使患者在HCT后面临更高风险。
