Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/130684
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dc.contributor.authorShanmuganathan, N.en
dc.contributor.authorPagani, I.S.en
dc.contributor.authorRoss, D.M.en
dc.contributor.authorPark, S.en
dc.contributor.authorYong, A.S.en
dc.contributor.authorBraley, J.A.en
dc.contributor.authorAltamura, H.K.en
dc.contributor.authorHiwase, D.K.en
dc.contributor.authorYeung, D.T.en
dc.contributor.authorKim, D.-.W.en
dc.contributor.authorBranford, S.en
dc.contributor.authorHughes, T.P.en
dc.date.issued2021en
dc.identifier.citationBlood, 2021; 137(9):1196-1207en
dc.identifier.issn0006-4971en
dc.identifier.issn1528-0020en
dc.identifier.urihttp://hdl.handle.net/2440/130684-
dc.description.abstractWith treatment-free remission (TFR) rapidly becoming the ultimate goal of therapy in chronic myeloid leukemia (CML), there is a need to develop strategies to maximise sustained TFR by improving our understanding of its key determinants. Chronic phase CML patients attempting TFR were evaluated to identify the impact of multiple variables on the probability of sustained TFR. Early molecular response dynamics were included as a predictive variable, assessed by calculating the patient-specific halving time of BCR-ABL1 after commencing tyrosine kinase inhibitor (TKI) therapy. Overall, 115 patients attempted TFR and had ≥12 months follow-up. The probability of sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, was 55%. The time taken for the BCR-ABL1 value to halve was the strongest independent predictor of sustained TFR: 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P<.001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR. A more rapid initial BCR-ABL1 decline after commencing TKI also correlated with an increased likelihood of achieving TFR eligibility. The association between sustained TFR and the time taken for BCR-ABL1 to halve after commencing TKI was validated using an independent dataset. These data support the critical importance of the initial kinetics of BCR-ABL1 decline for long-term outcomes.en
dc.description.statementofresponsibilityNaranie Shanmuganathan, Ilaria S. Pagani, David M. Ross, Sahee Park, Agnes S.M. Yong, Jodi A. Braley, Haley K. Altamura, Devendra K. Hiwase, David T. Yeung, Dong-Wook Kim, Susan Branford, Timothy P. Hughesen
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.rights© 2021 by The American Society of Hematologyen
dc.subjectDisease remission; kinetics; leukemia; myelocytic; chronic; protein-tyrosine kinase inhibitor; follow-upen
dc.titleEarly BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemiaen
dc.typeJournal articleen
dc.identifier.doi10.1182/blood.2020005514en
pubs.publication-statusPublisheden
dc.identifier.orcidShanmuganathan, N. [0000-0001-5895-8797]en
dc.identifier.orcidPagani, I.S. [0000-0002-3216-2966]en
dc.identifier.orcidRoss, D.M. [0000-0001-7171-2935]en
dc.identifier.orcidYong, A.S. [0000-0001-9452-1533]en
dc.identifier.orcidHiwase, D.K. [0000-0002-6666-3056]en
dc.identifier.orcidYeung, D.T. [0000-0002-7558-9927]en
dc.identifier.orcidBranford, S. [0000-0002-1964-3626]en
dc.identifier.orcidHughes, T.P. [0000-0002-0910-3730]en
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