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儿童异基因造血干细胞移植后用于复发风险评估的长期供体嵌合状态监测

Long-Term Donor Chimerism Monitoring for Relapse Risk Assessment After Pediatric Allo-HSCT.

作者信息

Prażmo Anna, Skowera Paulina, Zaucha-Prazmo Agnieszka, Lejman Monika

机构信息

Student Scientific Society of Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland.

Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland.

出版信息

Appl Clin Genet. 2025 Jul 24;18:131-146. doi: 10.2147/TACG.S520646. eCollection 2025.

Abstract

OBJECTIVE

Allo-HSCT is a well-established treatment for several hematological malignancies. Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a significant problem and is associated with a poor prognosis and low overall survival. Chimerism analysis is one of the tools applied in post-transplant monitoring, as an increasing fraction of recipient cells after HSCT has been linked to a higher risk of relapse.

STUDY DESIGN

In this retrospective, single-centre study we have analysed the data of patients treated with allo-HSCT for a range of hematological malignancies in the Department of Paediatric Haematology, Oncology and Transplantology, Medical University of Lublin, Poland, between years 2002-2018.

RESULTS

For all 103 patients 3-years OS was 72.6 (95% CI: 64.3-82.0) and 3-years EFS was 72.0 (95% CI: 63.5-81.6). There were no differences in 3-years OS and EFS in group of patients who achieved FDC <14 and >14 days: 67.9 (95% CI: 57.4-80.3) vs 81.9 (95% CI: 69.7-96.2), p = 0.220 and 66.0 (95% CI: 55.3-78.7) vs 84.1 (95% CI: 72.3-97.9), p = 0.073, respectively. Early FDC achievement was not significantly associated with risk of relapse, p = 0.181. Based on multivariate Cox regression analysis AML/MDS increased risk of relapse 3x compared to ALL, HR = 2.72, CI95 [1.24-5.98], p = 0.013; PB/CB increased the risk nearly 3x compared to cells from BM, HR = 2.52, CI95 [1.12-5.65], p = 0.025.

CONCLUSION

In presented study, achieving early FDC was not associated with lower risk of relapse and had no impact on overall and event-free survival. However, the study presents a unique data of very early chimerism in a large cohort of paediatric patients with haematological malignancies treated within a single unit. Possible extensions to this study, to include analysing more data from a larger patient cohort, may allow us to determine the exact prognostic value of very early chimerism analysis to establish relevant cutoff values and risk thresholds for intervention.

摘要

目的

异基因造血干细胞移植(Allo-HSCT)是多种血液系统恶性肿瘤的成熟治疗方法。异基因造血干细胞移植后复发仍然是一个重大问题,与预后不良和总体生存率低相关。嵌合分析是移植后监测中应用的工具之一,因为造血干细胞移植后受者细胞比例增加与更高的复发风险相关。

研究设计

在这项回顾性单中心研究中,我们分析了2002年至2018年间在波兰卢布林医科大学儿科血液学、肿瘤学和移植学系接受异基因造血干细胞移植治疗一系列血液系统恶性肿瘤的患者数据。

结果

所有103例患者的3年总生存率(OS)为72.6(95%可信区间:64.3 - 82.0),3年无事件生存率(EFS)为72.0(95%可信区间:63.5 - 81.6)。在移植后14天内和超过14天达到完全供者嵌合(FDC)的患者组中,3年OS和EFS无差异:分别为67.9(95%可信区间:57.4 - 80.3)与81.9(95%可信区间:69.7 - 96.2),p = 0.220;以及66.0(95%可信区间:55.3 - 78.7)与84.1(95%可信区间:72.3 - 97.9),p = 0.073。早期达到FDC与复发风险无显著相关性,p = 0.181。基于多变量Cox回归分析,急性髓系白血病/骨髓增生异常综合征(AML/MDS)的复发风险比急性淋巴细胞白血病(ALL)高3倍,风险比(HR)= 2.72,95%置信区间[1.24 - 5.98],p = 0.013;外周血/脐血来源的细胞相比骨髓来源的细胞复发风险增加近3倍,HR = 2.52,95%置信区间[1.12 - 5.65],p = 0.025。

结论

在本研究中,早期达到FDC与较低的复发风险无关,对总体生存和无事件生存无影响。然而,该研究提供了在单个单位治疗的一大群儿科血液系统恶性肿瘤患者中非常早期嵌合的独特数据。本研究的可能扩展,包括分析来自更大患者队列的更多数据,可能使我们能够确定非常早期嵌合分析的确切预后价值,以建立相关的截断值和干预风险阈值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d325/12304447/cc4fb1d3c68c/TACG-18-131-g0001.jpg

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