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

: 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. : 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). : 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 = 41, dasatinib/nilotinib group = 28, TKI-naïve group = 171). : Both the cumulative incidence of aGvHD ( = 0.044) and cGvHD ( < 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%, = 0.044; 25.0% vs. 76.4% vs. 51.2%, < 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 ( = 0.018, = 0.004; < 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%, = 0.740). : The results of our study suggest that TKI treatment prior to allo-HCT may have a protective impact on immune-mediated outcomes.