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基于 SNP 的新一代测序 (SNP-NGS) 在 HLA 错配造血干细胞微移植后嵌合体和微嵌合体评估中的临床应用。

The clinical application of SNP-based next-generation sequencing (SNP-NGS) for evaluation of chimerism and microchimerism after HLA-mismatched stem cell microtransplantation.

机构信息

Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, People's Republic of China.

National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

出版信息

Int J Hematol. 2022 Nov;116(5):723-730. doi: 10.1007/s12185-022-03415-8. Epub 2022 Jul 8.

DOI:10.1007/s12185-022-03415-8
PMID:35802296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9588463/
Abstract

Genetic diagnostic methods for evaluation of chimerism after HSCT, such as STR-PCR and XY-FISH, have limited sensitivity. When donor chimerism is in the micro range (< 1%), deviations in the accuracy of assessment are the most significant disadvantage of these common methods. We developed a highly sensitive method that applies SNPs based on NGS in order to explore the value of donor cell microchimerism in microtransplantation (MST). This improved SNP-NGS approach has higher sensitivity (0.01-0.05%) and only requires a small amount of DNA (8-200 ng). We retrospectively analyzed the clinical data of 48 patients with AML who received HLA-mismatched stem cell MST at our center to assess the impact of microchimerism on clinical prognosis. Patients whose duration of microchimerism was > 10.5 months (median) had a relapse rate of 26.1%, and had better 5-year LFS and OS (73.4% and 82.6%). In contrast, patients whose duration of microchimerism was < 10.5 months had a higher relapse rate (69.6%), and their 5-year LFS and OS were 30.4% and 43.5%. In conclusion, duration of donor chimerism is highly valuable for assessment of survival and prognosis in patients with AML who have received HLA-mismatched stem cell MST, especially the intermediate-risk group.

摘要

用于评估 HSCT 后嵌合体的遗传诊断方法,如 STR-PCR 和 XY-FISH,其灵敏度有限。当供体嵌合体处于微范围(<1%)时,这些常用方法在评估准确性方面的偏差是最显著的缺点。我们开发了一种高度敏感的方法,该方法应用基于 NGS 的 SNP,以探索微移植(MST)中供体细胞微嵌合体的价值。这种改进的 SNP-NGS 方法具有更高的灵敏度(0.01-0.05%),并且仅需要少量 DNA(8-200ng)。我们回顾性分析了在我们中心接受 HLA 错配干细胞 MST 的 48 例 AML 患者的临床数据,以评估微嵌合体对临床预后的影响。微嵌合体持续时间>10.5 个月(中位数)的患者复发率为 26.1%,5 年 LFS 和 OS 更好(73.4%和 82.6%)。相比之下,微嵌合体持续时间<10.5 个月的患者复发率更高(69.6%),其 5 年 LFS 和 OS 分别为 30.4%和 43.5%。总之,供体嵌合体的持续时间对于评估接受 HLA 错配干细胞 MST 的 AML 患者的生存和预后非常有价值,尤其是对于中危组患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/5a68d44f512e/12185_2022_3415_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/1d80197831b7/12185_2022_3415_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/30d060ee2fd4/12185_2022_3415_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/5a68d44f512e/12185_2022_3415_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/1d80197831b7/12185_2022_3415_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/30d060ee2fd4/12185_2022_3415_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fd/9588463/5a68d44f512e/12185_2022_3415_Fig3_HTML.jpg

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