Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain
Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain
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DOI：
10.1182/blood.v98.10.3150
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发表时间：
2001-11-15
期刊：
影响因子：
20.3
通讯作者：
Frumento, G
中科院分区：
文献类型：
--
作者：
Ferrara, GB;Bacigalupo, A;Frumento, G
在接受非亲属供体骨髓移植的患者中，人类白细胞抗原I类重链中特定位置的氨基酸取代会对移植相关死亡率（TRM）产生不同的影响。通过人类白细胞抗原(HLA)-A、-B和-C位点的序列分型，对100名患者及其非亲属供体进行分型。所有配对均匹配DRB1、DRB3、DRB4、DRB5、DQA1和DQB1位点。40对在I类位点也匹配，60对在I类位点有一个或多个不匹配。单因素和双因素Cox分析发现，I类重链116位和114位的替换显著增加了TRM的风险。相反，当调整位置116和114时，多重错配数或氨基酸取代数与TRM之间没有关联。在多变量Cox分析中，预测TRM的变量包括输注细胞数、诊断（慢性髓性白血病[CML]或非CML）和116或152位氨基酸取代。在多变量Cox分析中，预测严重急性移植物抗宿主病（GVHD）的唯一变量是116位的替代。116位置换组（n = 37）与其他组（n = 63）相比，急性GVHD III-IV级、TRM和复发的精算风险分别为36%对14% （P = 0.01）、59%对28% （P = 0.001）和25%对31% （P = 0.4）。总之，这些数据表明，I类重链116位的替换增加了接受非亲属骨髓移植患者急性GVHD和TRM的风险。血。(C) 2001年由美国血液学会出版。
The hypothesis was tested that amino acid substitutions in specific positions within human leukocyte antigen class I heavy chain would have different impacts on transplant-related mortality (TRM) in patients receiving transplanted bone marrow from unrelated donors. One hundred patients and their unrelated donors were typed by sequence-based typing for the human leukocyte antigen (HLA)-A, -B, and -C loci. All pairs were matched for DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 loci. Forty pairs were also matched at class I, and 60 pairs had one or more mismatches at class I loci. It was found that substitutions at positions 116 and 114 of class I heavy chain significantly increased the risk for TRM in univariate and bivariate Cox analyses. Conversely, no association between number of multiple mismatches or number of amino acid substitutions and TRM was seen when positions 116 and 114 were adjusted for. Variables predictive of TRM in multivariate Cox analysis were number of cells infused, diagnosis (chronic myeloid leukemia [CML] or non-CML), and amino acid substitution at position 116 or 152. The only variable predictive of severe acute graft-versus-host disease (GVHD) in multivariate Cox analysis was substitution at position 116. Actuarial risk for acute GVHD grade III-IV, TRM, and relapse in pairs with substitutions at position 116 (n = 37) compared to other pairs (n = 63) was, respectively, 36% versus 14% (P = .01), 59% versus 28% (P = .001), and 25% versus 31 % (P = .4). In conclusion these data suggest that substitutions at position 116 of class I heavy chain increase the risk for acute GVHD and TRM in patients who receive transplanted bone marrow from unrelated donors. Blood. (C) 2001 by The American Society of Hematology.