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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2025-01-01
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| author | Ugo Giordano Agnieszka Piekarska Witold Prejzner Lidia Gil Jan Maciej Zaucha Joanna Kujawska Zuzanna Dybko Krzysztof Dudek Sebastian Giebel Jarosław Dybko |
| author_facet | Ugo Giordano Agnieszka Piekarska Witold Prejzner Lidia Gil Jan Maciej Zaucha Joanna Kujawska Zuzanna Dybko Krzysztof Dudek Sebastian Giebel Jarosław Dybko |
| author_sort | Ugo Giordano |
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| description | <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. |
| format | Article |
| id | doaj-art-a48e4aa1d07c46059df1890a1ef4f792 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-a48e4aa1d07c46059df1890a1ef4f7922025-01-24T13:24:14ZengMDPI AGBiomedicines2227-90592025-01-0113116310.3390/biomedicines13010163Impact 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 GroupUgo Giordano0Agnieszka Piekarska1Witold Prejzner2Lidia Gil3Jan Maciej Zaucha4Joanna Kujawska5Zuzanna Dybko6Krzysztof Dudek7Sebastian Giebel8Jarosław Dybko9Department and Clinic of Endocrinology and Internal Medicine, Wrocław University Hospital, 50-367 Wroclaw, PolandDepartment of Hematology and Transplantology, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Hematology and Transplantology, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 60-569 Poznan, PolandDepartment of Hematology and Transplantology, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 60-569 Poznan, PolandFaculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, PolandFaculty of Mechanical Engineering, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, PolandDepartment of Bone Marrow Transplantation and Oncohematology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, PolandDepartment of Hematology and Cellular Transplantation, Lower Silesian Oncology Center, 53-413 Wroclaw, Poland<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.https://www.mdpi.com/2227-9059/13/1/163allogeneic hematopoietic stem cell transplantationchronic myeloid leukemiatyrosine kinase inhibitorsimatinibdasatinibnilotinib |
| spellingShingle | Ugo Giordano Agnieszka Piekarska Witold Prejzner Lidia Gil Jan Maciej Zaucha Joanna Kujawska Zuzanna Dybko Krzysztof Dudek Sebastian Giebel Jarosław Dybko 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 Biomedicines allogeneic hematopoietic stem cell transplantation chronic myeloid leukemia tyrosine kinase inhibitors imatinib dasatinib nilotinib |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | allogeneic hematopoietic stem cell transplantation chronic myeloid leukemia tyrosine kinase inhibitors imatinib dasatinib nilotinib |
| url | https://www.mdpi.com/2227-9059/13/1/163 |
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