Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.
机构：[1]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[2]Department of Hematology, No. 960 Hospital of People's Liberation Army, Jinan, China.中国人民解放军联勤保障部队第九六〇医院[3]Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.[4]Tissuebank Biotechnology Co., Ltd, Shanghai, China.[5]Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.[6]Department of Hematology, 920th Hospital of Joint Logistics Support Force, Kunming, China.[7]Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Second Hospital of Dalian Medical University, Dalian, China.[8]Department of Hematology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.[9]Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.[10]Department of Hematology, Tianjin First Central Hospital, Tianjin, China.[11]Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China.[12]Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China.[13]Department of Hematology, First People's Hospital of Yunnan Province, Kunming University of Science and Technology Affiliated Kun Hua Hospital, Kunming, China.内科片血液内科云南省第一人民医院[14]Department of Hematology, Zhongshan Hospital of Xiamen University, Xiamen, China.[15]Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.[16]Department of Hematology, The 940th Hospital of the Joint Logistic Support Force of PLA, Lanzhou, China.[17]Department of Hematology, Linyi People's Hospital, Linyi, China.[18]Department of Hematology, The First Hospital of China Medical University, Shenyang, China.[19]Department of Hematology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China.[20]Engineering Technology Research Center of Cell Therapy and Clinical Translation, Shanghai Science and Technology Committee, Shanghai, China.
Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss-related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss-related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort [odds ratio (OR): 3.15, P = 0.021] and patients with myeloid malignancies (OR: 3.94, P = 0.021). A higher refined-disease risk index (OR: 6.91, P = 0.033) and donor-recipient ABO incompatibility (OR: 4.58, P = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.
基金：
This study was approved by the Ethics Review Committee of
Shanghai General Hospital (2021KY005).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|4 区医学
小类|4 区移植4 区医学：研究与实验4 区细胞与组织工程
最新[2023]版：
大类|4 区医学
小类|4 区细胞与组织工程4 区医学：研究与实验4 区移植
JCR分区：
出版当年[2021]版：
Q2TRANSPLANTATIONQ3CELL & TISSUE ENGINEERINGQ3MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q2MEDICINE, RESEARCH & EXPERIMENTALQ2TRANSPLANTATIONQ3CELL & TISSUE ENGINEERING
第一作者机构：[1]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[2]Department of Hematology, No. 960 Hospital of People's Liberation Army, Jinan, China.[3]Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.[20]Engineering Technology Research Center of Cell Therapy and Clinical Translation, Shanghai Science and Technology Committee, Shanghai, China.[*1]Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300382, China[*2]Department of Hematology, No. 960 Hospital of People’s Liberation Army, Jinan 250031, China.[*3]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China.
推荐引用方式(GB/T 7714)：
Wang Andi,Li Wenjun,Zhao Fei,et al.Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.[J].Cell Transplantation.2022,31:9636897221102902.doi:10.1177/09636897221102902.
APA：
Wang Andi,Li Wenjun,Zhao Fei,Zheng Zhongzheng,Yang Ting...&Song Xianmin.(2022).Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing..Cell Transplantation,31,
MLA：
Wang Andi,et al."Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.".Cell Transplantation 31.(2022):9636897221102902
