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Real-world clinical experience with NGS-based chimerism analyses in haematopoietic stem cell transplant patients

Authors
 Jin Ju Kim  ;  Soon Sung Kwon  ;  Yu Jeong Choi  ;  Yehyun Kang  ;  Yu Jin Park  ;  Saeam Shin  ;  Seung-Tae Lee  ;  Jong Rak Choi 
Citation
 BRITISH JOURNAL OF HAEMATOLOGY, Vol.207(2) : 475-483, 2025-08 
Journal Title
BRITISH JOURNAL OF HAEMATOLOGY
ISSN
 0007-1048 
Issue Date
2025-08
MeSH
0
Keywords
Adolescent ; Adult ; Aged ; Chimerism* ; Female ; Hematologic Neoplasms* / genetics ; Hematologic Neoplasms* / mortality ; Hematologic Neoplasms* / therapy ; Hematopoietic Stem Cell Transplantation* / methods ; High-Throughput Nucleotide Sequencing* / methods ; Humans ; Male ; Middle Aged ; Neoplasm, Residual / diagnosis ; Recurrence ; Retrospective Studies ; Transplantation Chimera* / genetics ; Young Adult
Abstract
HSC transplantation; chimerism analysis; minimal residual disease; next generation sequencing
Article Number
 10.1111/bjh.20191 
DOI
Next-generation sequencing (NGS) has improved the sensitivity of chimerism assays beyond the limitations of conventional short tandem repeat (STR) methods, enabling the detection of minimal recipient haematopoiesis after haematopoietic stem cell transplantation (HSCT). We evaluated the clinical utility of CASAL, an NGS-based chimerism assay, in routine practice. We retrospectively analysed 310 patients who underwent STR or CASAL chimerism testing between April 2021 and September 2023. CASAL provided significantly more informative markers than STR (median 18 vs. 6; p < 0.001). Among 260 CASAL samples with paired molecular minimal residual disease (MRD) data, concordance at the 10-4 threshold was ~84%. Low-level mixed chimerism (2%-5%) detected beyond 1 month post-HSCT was associated with impending relapse. In survival analyses, patients with both MC and MRD positivity (MC/MRD+) had the highest relapse risk across both platforms. Multivariable Cox regression confirmed MC/MRD+ as an independent predictor of relapse (hazard ratio 5.87, 95% CI: 1.17-29.57). CASAL enables sensitive chimerism monitoring and shows a strong correlation with molecular MRD and clinical outcomes. These findings support its clinical utility for individualized post-HSCT surveillance, especially in patients lacking leukaemia-specific molecular targets.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Soon Sung(권순성)
Kim, Jin Ju(김진주) ORCID logo https://orcid.org/0000-0001-9166-1848
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/207439
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