KIR/HLA受配体模式对血液病患者单份非血缘脐血移植预后的影响

OBJECTIVE: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT). METHODS: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n＝174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2). Group 2 (n＝96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2). RESULTS: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1–62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG). The ratio of neutrophil engraftment for group 1 and 2 were both 98.9％, the median time of neutrophil engraftment for group 1 and 2 was 16 (10–41) days vs 17 (11–33) days (P＝0.705). The ratio of platelet engraftment was 88.5％ for group 1 and 87.5％ for group 2, the median time of platelet engraftment was 35 (11–113) days vs 38.5 (13–96) days (P＝0.317). The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7％（95％CI 31.4％–45.9％）for group 1 and 50.0％ (95％CI 39.6％–59.6％) for group 2 (P＝0.075), but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P＝0.036). Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2): 17.7％ (95％CI 11.7％–24.9％) vs 22.7％ (95％CI 4.4％–32.2％) after 3 years (P＝0.288). The median follow-up time was 742 (335–2 512) days. The 3-year OS was 72.1％ for group 1 and 60.5％ for group 2 (P＝0.079). There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9 ％ (95％CI 56.2％–72.3％) vs 55.4％ (95％CI 44.4％–65.0％) (χ(2)＝3.027, P＝0.082)]. Non-relapse mortality for group 1 was 12.1％ (95％CI 7.7％–17.4％) and for group 2 was 16.7％ (95％CI 10.0％–24.8％) (P＝0.328). CONCLUSION: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.