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    EUTOS Score for Chronic Myelogenous Leukemia (CML)

    Predicts outcomes after CML treatments, specifically adjusted for tyrosine kinase treatments.
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    INSTRUCTIONS

    Use in newly-diagnosed patients before starting therapy.

    When to Use
    Pearls/Pitfalls
    Why Use

    Newly-diagnosed CML patients prior to discussions regarding prognosis and treatment options.

    • The EUTOS (European Treatment and Outcome Study) Score predicts survival and can also be used to predict the probability of complete cytogenetic response at 18 months.
    • Has better predictive value than the Sokal Score.
    • Spleen size estimation is subjective; however, that subjectivity is also included in other CML prognostic scores.
    • Developed in patients treated with imatinib, so outcomes may not apply with newer generation therapies.
    • Estimates response to therapy to, and survival on, the reference TKI (tyrosine kinase inhibitor) imatinib.
    • Only requires two values, which can be clinically detected prior to completing a bone marrow biopsy.
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    About the Creator
    Dr. Joerg Hasford
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    Next Steps
    Evidence
    Creator Insights

    Management

    Though there is no broad consensus on management, a conservative strategy is to treat low-risk patients with imatinib and reserve newer-generation TKIs for high risk patients.

    Critical Actions

    Can only be applied to a newly-diagnosed patient before starting therapy.

    Formula

    EUTOS Score = (7 × basophil) + (4 × spleen), where

    • “Basophil” is basophils as a percentage of peripheral blood leukocytes, and
    • “Spleen” is spleen size palpable below left costal margin, in cm.

    Probability of not achieving complete cytogenic response (CCyR) at 18 months = exp(−2.1007 + 0.0700 × basophils + 0.0402 × spleen size)/(1 + exp[−2.1007 + 0.0700 + basophils + 0.0402 × spleen size])

    Facts & Figures

    Interpretation:

    EUTOS Score

    Risk category

    5 year progression-free survival*

    CCyR at 18 months*

    ≤87

    Low

    90%

    86%

    >87

    High

    82%

    66%

    *Response rates based on imatinib treatment only.
    CCyR, complete cytogenetic response rate.

    Evidence Appraisal

    The original derivation of the EUTOS Score came from a retrospective analysis of 1,223 European patients in the European Leukemia Network CML registry. All patients were treated with imatinib and divided into a learning cohort and a validation cohort. The prediction is based on a surrogate endpoint for survival of complete cytogenetic response at 18 months, but was found to also predict progression-free survival (PFS).  

    An attempt to validate the score by a single institution found that the score was not predictive for survival (Jabbour 2012). There are six major studies showing the EUTOS score predicts outcomes (Hoffman 2012, Hoffman 2013, Tiribelli 2012, Breccia 2012, Uz 2013, Yahng 2012) and three studies showing that it does not (Marin 2011, Jabbour 2012, Yamamoto 2014).

    The EUTOS Score continues to evolve, with recent data from Pfirrmann et al (2016) showing that an EUTOS Long-Term Survival Score (ELTS) differentiated probability of death due to CML better than the original EUTOS Score.

    Literature

    Validation

    Research PaperHoffmann VS, Mayer J, Turkina AG, Hellmann A, Indrak K, Steegmann JL, Zaritskey A, Colita A, Lindoerfer D, Baccarani M. EUTOS score is also valid in CML patients not involved in clinical studies. Blood 2012;120:Abstract 3759.Research PaperHoffmann VS, Baccarani M, Lindoerfer D, et al. The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia 2013;27:2016–22.Research PaperTiribelli M, Bonifacio M, Calistri E, et al. EUTOS score identifies cases with poor outcome in patients with early chronic phase chronic myeloid leukemia, though not predictive for optimal response to imatinib. Blood 2012;120:Abstract 3778. Research PaperBreccia M, Finsinger P, Loglisci G, Latagliata R, Mancini M, Salaroli A, Serrao A, Zacheo I, Alimena G. The EUTOS score identifies chronic myeloid leukeamia patients with poor prognosis treated with imatinib first or second line. Leuk Res 2012;36:e209–10.Research PaperUz B, Buyukasik Y, Atay H, et al. EUTOS CML prognostic scoring system predicts ELN-based ‘event-free survival’ better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate. Hematology 2013;18:247–52.Research PaperYahng SA, Jang EJ, Choi SY, et al. Comparison of Sokal, Hasford and EUTOS scores in terms of long-term treatment outcome according to the risks in each prognostic model: a single center data analyzed in 255 early chronic phase chronic myeloid leukemia patients treated with frontline imatinib mesylate. Blood 2012;120:Abstract 2794.

    Other References

    Research PaperMarin D, Ibrahim AR, Goldman JM. European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. J Clin Oncol 2011;29:3944–5. Research PaperJabbour E, Cortes J, Nazha A, O’Brien S, Quintas-Cardama A, Pierce S, Garcia-Manero G, Kantarjian H. EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience. Blood 2012;119:4524–6.Research PaperYamamoto E, Fujisawa S, Hagihara M, et al. European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients. Cancer Sci. 2014;105(1):105-9.Research PaperPfirrmann M, Baccarani M, Saussele S, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30(1):48-56.
    Dr. Joerg Hasford

    About the Creator

    Joerg Hasford, MD, PhD, is a Professor of Medical Data Processing, Biometrics and Epidemiology at the University of Munich in Germany. He is the chairman of the Ethics Committee of the Bavarian Medical Association and the Working Group Medical Ethics Commissions in the Federal Republic of Germany. In 2000, he was awarded the Paul Martini Prize of the German Society of Medical computer science, Biometry and Epidemiology, Dr. Hasford has also published numerous articles and serves as an editor for Pharmacoepidemiology and Drug Safety publication.

    To view Dr. Joerg Hasford's publications, visit PubMed

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