人类嗜T淋巴细胞病毒1型（HTLV-1）携带者前病毒载量的长期动力学：确定成人T细胞白血病/淋巴瘤发生的风险

Long-term kinetics of proviral load in HTLV-1 carriers: defining risk for the development of adult T-cell leukemia/lymphoma.

作者信息

Jimbo Koji, Nojima Masanori, Toriuchi Keiko, Yamagishi Makoto, Nakashima Makoto, Yamano Yoshihisa, Uchimaru Kaoru, Nannya Yasuhito

机构信息

Division of Hematopoietic Disease Control, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan.

Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

出版信息

Biomark Res. 2025 Feb 26;13(1):34. doi: 10.1186/s40364-025-00747-5.

DOI:10.1186/s40364-025-00747-5

PMID:40012084

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11863581/

Abstract

BACKGROUND

Assessment of adult T-cell leukemia/lymphoma (ATL) development among human T-lymphotropic virus 1 (HTLV-1)-infected individuals (carriers) constitute a significant issue. A high HTLV-1 proviral load (PVL) in carriers has been used as a risk factor for ATL development and PVLs are considered to remain unchanged over time among carriers.

METHODS

This single-center analysis used a cohort from a prospective observational study of HTLV-1 carriers in Japan (JSPFAD). Carriers whose PVL was measured at least twice between October 2004 and March 2023 were included. We used trajectory analysis to construct a kinetic model of the PVL.

RESULTS

Analysis of 1371 samples from 252 carriers revealed a slight but significant increase in the PVL with age (P < 0.001). Trajectory analysis of PVL kinetics classified the carriers into six groups, in three of which increased over time. When we applied the model to 15 carriers who subsequently developed ATL, 12 (80%) were classified into the highest PVL group, with an estimated 15-year ATL development of 47.5% (95% confidence interval: 20.4-74.2%). Notably, younger patients are at greater risk of developing ATL if their PVL values are comparable. Our risk estimation model is available online ( https://atlriskpredictor.shinyapps.io/ATL_risk_calculator/ ).

CONCLUSIONS

This study demonstrated that the PVLs increases over time, allowing for prospective risk estimation for ATL development. Further validation is needed to assess the validity of this model.

TRIAL REGISTRATION

Retrospectively registered.

摘要

背景

评估人类嗜T淋巴细胞病毒1型（HTLV-1）感染个体（携带者）中成人T细胞白血病/淋巴瘤（ATL）的发生情况是一个重要问题。携带者中HTLV-1前病毒载量（PVL）高已被用作ATL发生的危险因素，且PVL在携带者中被认为随时间保持不变。

方法

这项单中心分析使用了来自日本HTLV-1携带者前瞻性观察研究（JSPFAD）的队列。纳入了在2004年10月至2023年3月期间PVL至少测量两次的携带者。我们使用轨迹分析构建PVL的动力学模型。

结果

对252名携带者的1371份样本进行分析发现，PVL随年龄略有但显著增加（P < 0.001）。PVL动力学的轨迹分析将携带者分为六组，其中三组随时间增加。当我们将该模型应用于随后发生ATL的15名携带者时，12名（80%）被归类为PVL最高组，估计15年ATL发生率为47.5%（95%置信区间：20.4 - 74.2%）。值得注意的是，如果年轻患者的PVL值相当，则发生ATL的风险更高。我们的风险估计模型可在线获取（https://atlriskpredictor.shinyapps.io/ATL_risk_calculator/）。