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Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib
oleh: Stefania Stella, Valentina Zammit, Silvia Rita Vitale, Maria Stella Pennisi, Michele Massimino, Elena TirrĂ², Stefano Forte, Antonio Spitaleri, Agostino Antolino, Sergio Siracusa, Vincenzo Accurso, Donato Mannina, Stefana Impera, Caterina Musolino, Sabina Russo, Alessandra Malato, Giuseppe Mineo, Maurizio Musso, Ferdinando Porretto, Bruno Martino, Francesco Di Raimondo, Livia Manzella, Paolo Vigneri, Fabio Stagno
Format: | Article |
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Diterbitkan: | MDPI AG 2019-05-01 |
Deskripsi
A reduction in <i>BCR-ABL1/ABL1<sup>IS</sup></i> transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple <i>BCR-ABL1</i> thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant <i>BCR-ABL1/ABL1<sup>IS</sup></i> transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR<sup>4</sup>; 71.5% vs. 16.1%) compared to individuals with <i>BCR-ABL1/ABL1<sup>IS</sup></i> levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with <i>BCR-ABL1/ABL1<sup>IS</sup></i> values >10% at 3 months but <1% at 6 months fared significantly better than individuals with <i>BCR-ABL1/ABL1<sup>IS</sup></i> <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; <i>p</i> < 0.001). Likewise, subjects with <i>BCR-ABL1/ABL1</i><sup>IS</sup> at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR<sup>4</sup> compared to patients with <i>BCR-ABL1/ABL1<sup>IS</sup></i> <10% at 3 months but >1% at 6 months (75% vs. 18.2%; <i>p</i> < 0.001). Finally, lower <i>BCR-ABL1/GUS<sup>IS</sup></i> transcripts at diagnosis were associated with <i>BCR-ABL1/ABL1<sup>IS</sup></i> values <1% at 6 months (<i>p</i> < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month <i>BCR-ABL1/ABL1<sup>IS</sup></i> level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.