HLA-A/B/C/DRB1/DQB1对非血缘造血干细胞移植影响的分析

本研究探讨供受者HLA-A/B/C/DRB1/DQB1等位基因不合的数目和位点对非血缘造血干细胞移植的影响。选取北京市道培医院101例非血缘造血干细胞移植病例,分别根据供受者HLA-A/B/C/DRB1/DQB1位点0-3个等位基因不合和HLA-C位点的不同,分组统计移植后1年以上总生存率、急性GVHD发生率和复发率。结果表明:①按供受者HLA等位基因水平10/10全相合组(30例)与9/10相合组(32例),8/10相合组(31例)以及7/10相合组(8例)分组比较,10/10和9/10组的1年以上总活存率(OS)较8/10组(78%and 82%vs50%,p=0.39)增多;10/10组、9/10组和8/10组复发率为16%和18%vs20%;10/10组没有Ⅱ度以上GVHD发生,9/10和8/10组10%左右。7/10组虽然病例数少,缺乏统计学意义,但结果证实安全有效。②)对比HLA-C位点等位基因不合组与HLA-10/10全合组,HLA-C不合组有延长1年以上总生存率(77%vs85%,p=0.30),降低复发率的趋势(8%vs17%,p=0.47),其Ⅱ度以上GVHD发生率明显增高,统计学有明显差异(0%vs25%,p=0.006)。③按抑制性KIR的配体HLA-C1/C2将HLA-10/10组与HLA-C一个等位基因不合组按供受者HLA-C1/C2 match和mismatch分为两组(37例和5例),发现1年以上总生存率、复发率,GVHD发生率无明显差异(78%vs80%,14%vs20%,和5%vs20%)。结论:供受者HLA-A/B/C/DRB1/DQB1等位基因不相合数目0-2个情况下,数目越少,1年以上生存率越高,复发率和急性GVHD无明显差异。7/10组是安全的。HLA-C不相合组GVHD发生率明显增高,有减少复发和延长生存率的趋势,但其原因是否与抑制性KIR与其配体HLA-C1/C2有关,尚待研究。

Influence of HLA-A/B/C/DRB1/DQB1 on Unrelated Donor Hematopoietic Stem Cell Transplantation

This study was purposed to explore the influence of number and locus of HLA allele mismatch on unrela-ted donor hematopoietic stem cell transplantation（URHSCT） in Chinese Han population.Total 10 alleles within the HLA-A/B/C/DRB1/DQB1 loci were analyzed by PCR-SSP for 101 pairs of donor and recipients who received URHSCT.101 cases of URHSCT were divided into four groups： HLA-allele 10/10 match（n=30）,9/10（n=32）,8/10（n=31） and 7/10 match（n=8）.The correlation of the HLA with overall survival（OS≥ 1 year）,incidence of acute GVHD（aGVHD） of grade II to IV and relapse rate of primary diseases were evaluated.The results showed that（1）The OS rates in HLA-10/10 and 9/10 groups were higher than that in HLA-8/10 match group（78% and 82% vs 50%,p=0.39）;incidence of aGVHD in the HLA-10/10 were lower than that in HLA-9/10 and HLA-8/10 group（0% vs 10% and 10%;p=0.28）;relapse rates among the 3 groups were close（16%,18% and 20%,respectively）.Although there were only 8 cases in HLA-7/10 match URHSCT,the data indicated that they were safe and effective;（2） Compared to the HLA-10/10 match URHSCT（n=30）,the HLA-C mismatch URHSCT（n=12） harbored higher incidence of severe aGVHD（0% vs 25%,p=0.006）,longer OS（77% vs 85%,p=0.30）,and tendency to low relapse rate（8% vs17%,p=0.47）;（3） According to HLA-C1/C2,the ligands of inhibitory KIR,the 42 cases of HLA-10/10 match URHSCT and HLA-C mismatch URHSCT were grouped into donor/recipient HLA-C1/C2 match and mismatch subgroups. There was no difference between the two subgroups for OS,incidence of aGVHD and relapse rate（78% vs 80%,14% vs 20%,and 5% vs 20%）.It is concluded that for 0 to 2 locus of HLA allele mismatch in URHSCT,the fewer mismatch numbers,the longer OS,but with similar aGVHD incidence and the relapse rate;triple HLA allele mismatch（HLA-7/10match） is safe in URHSCT.The HLA-C mismatch may be related to higher incidence of aGVHD and lower relapse rate and prolonged OS,remaining to be further studied.