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HLA-DPB1在非亲缘供者造血细胞移植中的重要性。

The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation.

作者信息

Shaw Bronwen E, Gooley Theodore A, Malkki Mari, Madrigal J Alejandro, Begovich Ann B, Horowitz Mary M, Gratwohl Alois, Ringdén Olle, Marsh Steven G E, Petersdorf Effie W

机构信息

Anthony Nolan Research Institute, London, UK.

出版信息

Blood. 2007 Dec 15;110(13):4560-6. doi: 10.1182/blood-2007-06-095265. Epub 2007 Aug 28.

Abstract

Hematopoietic cell transplantation (HCT) from an HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donor is a well-recognized life-saving treatment modality for patients with hematologic disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplantation outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse, and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-matched or -mismatched donor. There was a statistically significantly higher risk of both grades 2 to 4 aGVHD (odds ratio [OR] = 1.33; P < .001) and grades 3 to 4 aGVHD (OR = 1.26; P < .001) after HCT from an HLA-DPB1-mismatched donor compared with a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (hazard ratio [HR] = 0.82; P = .01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplantation will aid in more precise risk stratification for the individual patient.

摘要

来自人类白细胞抗原A(HLA-A)、B(HLA-B)、C(HLA-C)、DRB1(HLA-DRB1)和DQB1(HLA-DQB1)等位基因匹配的无关供体的造血细胞移植(HCT)是治疗血液系统疾病患者公认的挽救生命的治疗方式。具有临床意义的急性移植物抗宿主病(aGVHD)的发病率和死亡率仍然是一个限制因素。通过HLA-DP供体匹配能在多大程度上改善移植结局尚不清楚。在5929例接受了来自HLA-A、HLA-B、HLA-C、HLA-DRB1和HLA-DQB1匹配或不匹配供体的清髓性HCT的患者中,确定了与HLA-DPB1等位基因错配相关的aGVHD、复发和死亡风险。与匹配供体相比,接受HLA-DPB1错配供体HCT后,2至4级aGVHD(优势比[OR]=1.33;P<.001)和3至4级aGVHD(OR=1.26;P<.001)的风险在统计学上均显著更高。aGVHD风险增加的同时,疾病复发在统计学上显著降低(风险比[HR]=0.82;P=.01)。HLA-DPB1作为一种经典的移植抗原发挥作用。与HLA-DPB1错配相关的GVHD风险增加伴随着较低的复发风险。移植前了解DPB1匹配状态将有助于对个体患者进行更精确的风险分层。

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