Biomarker research · 2025
Long-term kinetics of proviral load in HTLV-1 carriers: defining risk for the development of adult T-cell leukemia/lymphoma.
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Jimbo Koji, Nojima Masanori, Toriuchi Keiko, Yamagishi Makoto, Nakashima Makoto, Yamano Yoshihisa, Uchimaru Kaoru, Nannya Yasuhito
Аннотация
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.
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.