Impact of First- and Second-Generation Tyrosine Kinase Inhibitors on the Development of Graft-Versus-Host Disease in Individuals with Chronic Myeloid Leukemia: A Retrospective Analysis on Behalf of the Polish Adult Leukemia Group

<b>Background</b>: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell tran...

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Main Authors: Ugo Giordano, Agnieszka Piekarska, Witold Prejzner, Lidia Gil, Jan Maciej Zaucha, Joanna Kujawska, Zuzanna Dybko, Krzysztof Dudek, Sebastian Giebel, Jarosław Dybko
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/163
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Summary:<b>Background</b>: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes has not been thoroughly explored. <b>Objectives</b>: The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD). <b>Methods</b>: In our retrospective analysis, we included 240 patients treated between 1993 and 2013 and divided them into three groups according to the therapy administered prior to haploidentical, matched-related, or matched-unrelated donor allo-HCT (imatinib group <i>n</i> = 41, dasatinib/nilotinib group <i>n</i> = 28, TKI-naïve group <i>n</i> = 171). <b>Results</b>: Both the cumulative incidence of aGvHD (<i>p</i> = 0.044) and cGvHD (<i>p</i> < 0.001) in individuals receiving second-generation TKIs (2G-TKIs) prior to allo-HCT were decreased compared to patients receiving no TKIs or imatinib (IMA) (40.7% vs. 61.4% vs. 70.7%, <i>p</i> = 0.044; 25.0% vs. 76.4% vs. 51.2%, <i>p</i> < 0.001, respectively). In the case of the 2G-TKI cohort, the number of low-grade aGvHD and cGvHD was significantly lower compared to the IMA and TKI-naïve groups (<i>p</i> = 0.018, <i>p</i> = 0.004; <i>p</i> < 0.001 versus TKI-naïve, respectively). In terms of 3-year overall survival (OS), there were no important variations between TKI-naïve, IMA, and 2G-TKI (55% vs. 49.9% vs. 69.6%, <i>p</i> = 0.740). <b>Conclusions</b>: The results of our study suggest that TKI treatment prior to allo-HCT may have a protective impact on immune-mediated outcomes.
ISSN:2227-9059