Verneris Michael R, Miller Jeffrey S, Hsu Katherine C, Wang Tao, Sees Jennifer A, Paczesny Sophie, Rangarajan Hemalatha, Lee Dean A, Spellman Stephen R, Lee Stephanie J
Children's Hospital Colorado-University of Colorado, Aurora, CO.
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN.
Blood Adv. 2020 Apr 14;4(7):1350-1356. doi: 10.1182/bloodadvances.2019001284.
Multiple models of donor killer immunoglobulin receptor (KIR) alloreactivity or KIR genotype have been reported to be protective against leukemia relapse after allogeneic transplantation. However, few studies have addressed this topic in the pediatric population. Here, we assessed the outcomes of allogeneic transplantation in children with acute lymphoblastic leukemia (ALL; n = 372) or acute myeloid leukemia (AML; n = 344) who received unrelated donor (URD) transplantation and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005 to 2016. As expected in this pediatric population, most patients underwent myeloablative conditioning while in remission and with bone marrow as a stem cell source. We tested KIR ligand mismatch, KIR gene content (centromeric [Cen] B), KIR2DS1 mismatching, and Cen B/telomeric A using Cox regression models and found that none were significantly associated with either relapse or disease-free survival when considering the entire cohort of patients (ALL and AML), AML, or ALL separately. Moreover, there was no significant association with outcomes in the in vivo T-cell-depleted (ie, serotherapy) cohort. This study, which is the largest analysis of donor KIR in the pediatric acute leukemia population, does not support the use of KIR in the selection of URDs for children undergoing T-replete transplantation.
已有多种供体杀伤细胞免疫球蛋白受体（KIR）同种异体反应性模型或KIR基因型被报道可预防异基因移植后白血病复发。然而，很少有研究在儿科人群中探讨这一话题。在此，我们评估了2005年至2016年期间接受非亲缘供体（URD）移植并向国际血液和骨髓移植研究中心（CIBMTR）报告的急性淋巴细胞白血病（ALL；n = 372）或急性髓系白血病（AML；n = 344）患儿的异基因移植结局。正如在该儿科人群中所预期的那样，大多数患者在缓解期接受了清髓性预处理，并以骨髓作为干细胞来源。我们使用Cox回归模型测试了KIR配体错配、KIR基因含量（着丝粒[Cen]B）、KIR2DS1错配以及Cen B/端粒A，发现在考虑所有患者队列（ALL和AML）、AML或ALL时，这些因素均与复发或无病生存无显著相关性。此外，在体内T细胞清除（即血清疗法）队列中，这些因素与结局也无显著相关性。这项研究是对儿科急性白血病人群中供体KIR进行的最大规模分析，不支持在为接受T细胞充足移植的儿童选择URD时使用KIR。
