IL-18基因启动子区单核苷酸多态性在恶性血液病患者HLA匹配同胞供者异基因造血干细胞移植中的临床意义

IL-18 single nucleotide polymorphisms in hematologic malignances with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation

目的研究IL-18基因启动子区单核苷酸多态性（SNP）对恶性血液病患者HLA匹配同胞供者异基因造血干细胞移植（allo．HSCT）造血重建、并发症及生存的影响。方法93例恶性血液病患者纳人研究。采用序列特异性引物聚合酶链反应（PCR．ssP）法检测供受者IL．18基因SNP．607C／A和．137G／C，分析供受者IL．18不同基因型对患者造血重建速度、移植物抗宿主病（GVHD）发生率、感染发生率、移植相关死亡（TRM）和无病生存（DFS）率的影响。结果供者．137G／G与G／C＋C／C组比较，allo-HSCT后患者中位粒细胞重建时间较短[15（11～23）d对17（11-24）d，P=0．010]，中位血小板重建时间差异无统计学意义[20（11-46）d对20（7～38）d，P=0．844]，广泛型慢性GvHD（cGvHD）发生率较高（20．6％对3．3％，P=0．029）；供者．607C／C组广泛型cGVHD发生率高于-607C／A＋A／A组（31．6％对10．8％，P=0．024）；受者．607C／C组广泛型cGVHD发生率高于．607C／A＋A／A组（33．3％对10．7％，P=0.016）。不同供受者IL-18基因型组间复发率、TRM、DFS率差异均无统计学意义（P值均〉0．05）。结论选择IL-18．137G／G基因型供者有助于恶性血液病患者HLA匹配同胞供者allo—HSCT后粒细胞造血重建，但广泛型cGVHD发生率较高。

Objective To explore the impact of interleukin-18 （IL-18） single nucleotide polymorphisms on outcomes of hematologic malignances with HLA-matched sibling donor hematopoietic stem cell transplantation （allo-HSCT）. Methods Single-nucleotide polymorphisms in IL-18 promoter was detected by PCR- sequencespecific primer analysis （PCR-SSP） in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease （GVHD） and infections, transplant related mortality （TRM）, and disease free survival （DFS） were analyzed. Results In comparison with- 137 G/C＋C/C donor genotype, patients with- 137 G/G donor genotype had shorter duration of neutrophil recovery [15 （11-23） days vs 17 （11-24） days, P=-0.01], higher incidence of extensive chronic GVHD （20.6% vs 3.3%, P=0.029）, but no difference in the interval ofplatelet recovery [ 20 （ 11- 46） days vs 20 （7- 38） days, P=0.844 ]. The incidence of extensive chronic GVHD in - 607 C/C donor genotype （31.6%） was significantly higher than that （10.8%） in C/A＋A/A donor genotype （P=- 0.024）. Recipients with -607 C/C genotype also had higher incidence （33.3%） of extensive chronic GVHD than those with C/A＋A/A genotype （10.7%, P=-0.016）. There were no differences in acute GVHD, TRM, and DFS between different genotypes. Conclusion IL-18- 137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo- HSCT.