Lineage-specific detection of residual disease predicts relapse in chronic myeloid leukemia patients stopping therapy

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dc.contributor.authorPagani, I.S.
dc.contributor.authorShanmuganathan, N.
dc.contributor.authorDang, P.
dc.contributor.authorSaunders, V.A.
dc.contributor.authorGrose, R.
dc.contributor.authorKok, C.H.
dc.contributor.authorJames, J.
dc.contributor.authorTolland, M.
dc.contributor.authorBraley, J.A.
dc.contributor.authorAltamura, H.K.
dc.contributor.authorYeung, D.T.
dc.contributor.authorBranford, S.
dc.contributor.authorYong, A.S.
dc.contributor.authorHughes, T.P.
dc.contributor.authorRoss, D.M.
dc.date.issued2023
dc.description.abstractPatients with chronic myeloid leukemia who are eligible for treatment-free remission (TFR) may still relapse after tyrosine kinase inhibitor (TKI) cessation. There is a need for accurate predictors of outcome to enable patients with a favorable profile to proceed while avoiding futile attempts. Sensitive detection of residual disease in total leukocytes at treatment cessation is associated with relapse but is not highly discriminatory, likely because it is a composite measure of residual leukemia derived from different cell lineages, whereas only some lineages are relevant for relapse. We prospectively measured BCR::ABL1 DNA as a predictive yes/no binary test in 5 cellular fractions from 48 patients meeting conventional criteria for TKI discontinuation. The median BCR::ABL1 DNA level was higher in granulocytes and T cells, but not in other lineages, in patients who relapsed. Among the 40 patients undergoing their first TFR attempt, we defined 3 groups with differing relapse risk: granulocyte-positive group (100%), granulocyte-negative/T-cell–positive group (67%), and granulocyte-negative /T-cell–negative group (25%). These data show the critical importance of lineage-specific assessment of residual disease in the selection of patients who can attempt to achieve TFR with a high expectation of success and, concurrently, defer patients who have a high probability of relapse.
dc.description.statementofresponsibilityIlaria S. Pagani, Naranie Shanmuganathan, Phuong Dang, Verity A. Saunders, Randall Grose, Chung H. Kok, Jane James, Molly Tolland, Jodi A. Braley, Haley K. Altamura, David T. Yeung, Susan Branford, Agnes S. M. Yong, Timothy P. Hughes, and David M. Ross
dc.identifier.citationBlood, 2023; 142(25):2192-2197
dc.identifier.doi10.1182/blood.2023021119
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidPagani, I.S. [0000-0002-3216-2966]
dc.identifier.orcidShanmuganathan, N. [0000-0001-5895-8797]
dc.identifier.orcidKok, C.H. [0000-0002-3181-7852]
dc.identifier.orcidTolland, M. [0000-0002-0955-2499]
dc.identifier.orcidYeung, D.T. [0000-0002-7558-9927]
dc.identifier.orcidBranford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]
dc.identifier.orcidHughes, T.P. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.orcidRoss, D.M. [0000-0001-7171-2935]
dc.identifier.urihttps://hdl.handle.net/2440/142089
dc.language.isoen
dc.publisherAmerican Society of Hematology (ASH Publications)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1138935
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2007908
dc.rights© 2023 by The American Society of Hematology
dc.source.urihttps://www.sciencedirect.com/science/article/pii/S000649712302061X?via%3Dihub
dc.subjectChronic myeloid leukemia
dc.subject.meshHumans
dc.subject.meshRecurrence
dc.subject.meshFusion Proteins, bcr-abl
dc.subject.meshDNA
dc.subject.meshProtein Kinase Inhibitors
dc.subject.meshRemission Induction
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive
dc.titleLineage-specific detection of residual disease predicts relapse in chronic myeloid leukemia patients stopping therapy
dc.typeJournal article
pubs.publication-statusPublished

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