异基因造血干细胞移植供患者HLA基因确认分型中存在的问题及解决策略

Challenges and solutions in current human leukocyte antigen confirmatory typing of hematopoietic stem cell transplantation

由于人类白细胞抗原(HLA)在异基因造血干细胞移植中的重要性,临床移植中心对HLA基因分型结果的准确性提出了较高的要求。本文针对本实验室在进行HLA基因确认分型工作中发现的一些问题,并基于国家标准、行业标准等,结合我国HLA基因分型技术开展的实际情况,探讨了在造血干细胞移植前对患者和潜在供者进行HLA基因确认分型的必要性。通过回顾性分析本实验室确认分型过程中所发现的患者/供者初次分型错误,分析了检验前、中、后各个阶段中,HLA基因分型工作可能存在哪些问题及关键节点,针对问题的原因归类为人为因素、技术方法局限性、患者自身疾病和治疗三大类,并分别提出具体的解决策略;并且在针对不同问题原因提出的具体建议和解决策略的基础上,思考如何才能做好HLA确认分型以及HLA在我国未来的发展方向。

The impact of human leukocyte antigen(HLA)on hematopoietic stem cell transplantation(HSCT)necessitates high precision in HLA genotyping.Confirmatory typing for patients and their related or unrelated donors before HSCT is critical.This study seeks to standardize HLA confirmatory typing in laboratories by examining the current state of HLA genotyping in the country,building upon the National Standards and Industrial Standards for HLA,and highlighting the significance of confirmatory typing for patients and potential donors prior to HSCT.A retrospective analysis over a decade reveals initial typing errors,indicating potential issues and critical considerations in pre-analytical,analytical,and post-analytical stages.Problems are attributed to three main causes:(1)random human errors,including technical mistakes,sample mix-up,and transcription inaccuracies;(2)limitations of technical methods,such as the varied sequence ranges between confirmatory and initial typing;(3)patient factors,involving high tumor burden,the influence of certain drugs on HLA genotyping results,and the second transplantation.Solutions are proposed for these problems,along with recommendations to standardize HLA confirmatory typing.