02adf9da9309c667094b2da25e470961 302121.pdf e0ccdd5eea89055443ecb38e519cdcf1ae1589b1 302121.pdf 45de5b179977d36ab52144b1e15688c9f7c68507afdb18621961a0ee48d84d1a 302121.pdf Title: e14a2 Transcript Favors Treatment-Free Remission in Chronic Myeloid Leukemia When Associated with Longer Treatment with Tyrosine Kinase Inhibitors and Sustained Deep Molecular Response Subject: e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain in the so-called treatment-free remission (TFR) phase, but biological factors associated with these goals are not well established. This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI). Patients treated at least 119 months with IM presented less post-discontinuation relapse than those that discontinued IM before 119 months (p = 0.005). In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript. Keywords: chronic myeloid leukemia; BCR::ABL1 transcript type; tyrosine kinase inhibitors; discontinuation; treatment free remission Author: Sílvia Marcé, Aleix Méndez, Blanca Xicoy, Natalia Estrada, Marta Cabezón, Antonella Luciana Sturla, Miriam Ratia García, Anna Angona, Paula Amat, Silvia Escribano Serrat, Emilia Scalzulli, Mireia Morgades, Alicia Senín, Juan Carlos Hernández-Boluda, Francisca Ferrer-Marín, Eduardo Anguita, Montserrat Cortés, Esther Plensa, Massimo Breccia, Valentín García-Gutierrez and Lurdes Zamora Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Feb 8 03:35:34 2024 CET ModDate: Thu Feb 8 03:45:30 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2237890 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- 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0 HNKEGF+PalatinoLinotype TrueType MacRoman yes yes no 260 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-07 02:44:01 CET RepresentationInformation: 302121.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-06 14:02:12 CET Size: 2237890 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 502 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patient Samples Destination: subsection.2.1 Item: Title: Cytogenetic Studies Destination: subsection.2.2 Item: Title: Determination of BCR::ABL1 Transcript Type and Real-Time Quantitative Polymerase Chain Reaction Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Effect of Transcript Type on DMR and TFR in IM-Treated Patients Destination: subsection.3.1 Item: Title: IM Treatment Duration and Influence of sDMR on TFR, and by Transcript Type Destination: subsection.3.2 Item: Title: Influence of Age, the Sokal and ELTS Scores on DMR and TFR in IM-Treated Patients Destination: subsection.3.3 Item: Title: Patients Treated with 2G-TKI as Frontline Treatment Destination: subsection.3.4 Item: Title: Effect of Transcript Type on DMR and TFR in 2G-TKI-Treated Patients Destination: subsection.3.5 Item: Title: 2G-TKI Treatment Duration and Influence of sDMR on TFR Destination: subsection.3.6 Item: Title: Influence of Age and the Sokal and ELTS Scores on DMR and TFR in 2G-TKI-Treated Patients Destination: subsection.3.7 Item: Title: Discussion and Conclusions Destination: section.4 Item: Title: References Destination: appendix.A. Info: Title: e14a2 Transcript Favors Treatment-Free Remission in Chronic Myeloid Leukemia When Associated with Longer Treatment with Tyrosine Kinase Inhibitors and Sustained Deep Molecular Response Author: Sílvia Marcé, Aleix Méndez, Blanca Xicoy, Natalia Estrada, Marta Cabezón, Antonella Luciana Sturla, Miriam Ratia García, Anna Angona, Paula Amat, Silvia Escribano Serrat, Emilia Scalzulli, Mireia Morgades, Alicia Senín, Juan Carlos Hernández-Boluda, Francisca Ferrer-Marín, Eduardo Anguita, Montserrat Cortés, Esther Plensa, Massimo Breccia, Valentín García-Gutierrez and Lurdes Zamora Subject: e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain in the so-called treatment-free remission (TFR) phase, but biological factors associated with these goals are not well established. This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI). Patients treated at least 119 months with IM presented less post-discontinuation relapse than those that discontinued IM before 119 months (p = 0.005). In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript. 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