ELTS Score and Early "Warning" Define a Two-Stage Risk Framework for Failure-Free Survival in Chronic-Phase CML

Risk stratification to predict treatment failure in chronic-phase chronic myeloid leukemia (CP-CML) remains an important challenge in the tyrosine kinase inhibitor (TKI) era. We conducted a pooled analysis of 710 newly diagnosed CP-CML patients enrolled in the prospective JALSG CML212 and New TARGET studies, approximately 80% of whom received second-generation TKIs (2G-TKIs) as first-line therapy, to identify predictors of failure-free survival (FFS). In this study, we incorporated the ELN 2025-defined "Warning" category as an initial adverse state in the definition of FFS events and evaluated transitions to "Unfavorable". Within this framework, the EUTOS long-term survival (ELTS) score consistently stratified FFS whether treatment failure included both "Warning" and "Unfavorable" events or was restricted to "Unfavorable". Among patients treated with 2G-TKIs, ELTS demonstrated superior time-dependent discrimination compared with Sokal and remained the baseline predictor of initial treatment failure. Importantly, once "Warning" occurred, baseline ELTS no longer predicted deterioration. Instead, attainment of "Warning" within 6 months after TKI initiation independently predicted transition from "Warning" to "Unfavorable" (HR 7.31, 95% CI 2.94-18.2; p<0.001). These findings distinguish baseline risk from post-milestone disease evolution and support a two-stage risk framework integrating baseline ELTS stratification with "Warning" timing to guide dynamic risk-adapted management in CP-CML.

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Journal
Blood Advances
Published
2026-08-14
DOI
https://doi.org/10.1182/bloodadvances.2026021073
Primary Topic
Chronic Myeloid Leukemia Treatments
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article
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article

ELTS Score and Early "Warning" Define a Two-Stage Risk Framework for Failure-Free Survival in Chronic-Phase CML

Ritsuro Suzuki, Hitoshi Kiyoi, Takaaki Ono, Shigeki Ohtake et al.
Blood Advances
Chronic Myeloid Leukemia Treatments
article

ELTS Score and Early "Warning" Define a Two-Stage Risk Framework for Failure-Free Survival in Chronic-Phase CML

Ritsuro Suzuki, Hitoshi Kiyoi, Takaaki Ono, Shigeki Ohtake, Kazuhito Yamamoto, Emiko Sakaida, Shin Fujisawa, Kazunori Ohnishi, Yoji Ogasawara, Itaru Matsumura, Yoshiko Atsuta, Yukio Kobayashi, Naoto Takahashi, Toshihiro Miyamoto, Chiaki Nakaseko, Yosuke Minami, Kazuhiko Kakihana, Fumisato Takagi, Tetsuzo Tauchi, Noriyoshi Iriyama, Tatsuya Kawaguchi, Masahiro Kizaki, Masaya Okada, Yasushi Miyazaki, Katsumichi Fujimaki
article en

Abstract

Risk stratification to predict treatment failure in chronic-phase chronic myeloid leukemia (CP-CML) remains an important challenge in the tyrosine kinase inhibitor (TKI) era. We conducted a pooled analysis of 710 newly diagnosed CP-CML patients enrolled in the prospective JALSG CML212 and New TARGET studies, approximately 80% of whom received second-generation TKIs (2G-TKIs) as first-line therapy, to identify predictors of failure-free survival (FFS). In this study, we incorporated the ELN 2025-defined "Warning" category as an initial adverse state in the definition of FFS events and evaluated transitions to "Unfavorable". Within this framework, the EUTOS long-term survival (ELTS) score consistently stratified FFS whether treatment failure included both "Warning" and "Unfavorable" events or was restricted to "Unfavorable". Among patients treated with 2G-TKIs, ELTS demonstrated superior time-dependent discrimination compared with Sokal and remained the baseline predictor of initial treatment failure. Importantly, once "Warning" occurred, baseline ELTS no longer predicted deterioration. Instead, attainment of "Warning" within 6 months after TKI initiation independently predicted transition from "Warning" to "Unfavorable" (HR 7.31, 95% CI 2.94-18.2; p<0.001). These findings distinguish baseline risk from post-milestone disease evolution and support a two-stage risk framework integrating baseline ELTS stratification with "Warning" timing to guide dynamic risk-adapted management in CP-CML.

Blood Advances
Kanazawa University (JP), Nihon University (JP), Jikei University School of Medicine (JP), Kansai Medical University (JP), Hamamatsu University (JP), Kumamoto Health Science University (JP), Shimane University (JP), Akita University (JP), Fujisawa City Hospital (JP), Yokohama City University Medical Center (JP), Tokyo Metropolitan Komagome Hospital (JP), Hamamatsu University School of Medicine (JP), Shubun University (JP), Chiba University Hospital (JP), Kanazawa University Hospital (JP), Aichi Cancer Center (JP), National Cancer Center Hospital East (JP), Shimane University Hospital (JP), The Japanese Data Center for Hematopoietic Cell Transplantation (JP), Midorigaoka Hospital (JP), Social Insurance Saitama Chuo Hospital (JP), Nadogaya Hospital (JP), Nagasaki University (JP), Nagoya University (JP), International University of Health and Welfare (JP), Saitama Medical University (JP), Yokohama City University (JP), Kindai University (JP)
Reduced inequalities
Openalex Percentile: Top 10%
Chronic Myeloid Leukemia Treatments
DOIOpen Access PDFOpenAlex
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