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Abstract
Clonal hematopoiesis (CH) is a risk factor for the development of therapy-related myelodysplastic syndromes (tMDS) and acute myeloid leukemia (tAML). Adoption of targeted-immunotherapeutics since 2011, may alter the risk of CH progression to tMDS/AML. To study this, we evaluated risk of tMDS and tAML in 667 588 ≥ 1-year survivors of non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), melanoma and multiple-myeloma (MM) diagnosed during: 2000–2005, 2006–2010 and 2011–2016. The risk of tMDS increased significantly after NSCLC across all time periods (Ptrend = 0.002) while tAML risk decreased from 2006–2010 to 2011–2016, coinciding with increasing use of non-chemotherapeutic agents. tAML risk after RCC decreased (Ptrend = 0.007) whereas tMDS risk did not significantly change over time. After melanoma, tMDS and tAML risks were similar to the general population. tMDS and tAML risk after MM increased from the first to second time-period, however, only risk of tMDS decreased during last period. We report diverging trends in the risk of tAML and tMDS after adoption of modern cancer therapies for specific cancers. It is imperative to further explore impact of contemporary treatment strategies on clonal evolution. Modern treatments via their discrete mechanism of actions on pre-existing CH may alter the risk of subsequent tMDS and tAML.
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1 Roswell Park Comprehensive Cancer Center, Department of Medicine, Buffalo, USA (GRID:grid.240614.5) (ISNI:0000 0001 2181 8635); Cleveland Clinic, Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725); Roswell Park Comprehensive Cancer Center, Buffalo, USA (GRID:grid.240614.5) (ISNI:0000 0001 2181 8635)
2 Roswell Park Comprehensive Cancer Center, Department of Medicine, Buffalo, USA (GRID:grid.240614.5) (ISNI:0000 0001 2181 8635)
3 Cleveland Clinic Florida, Department of Hematology and Medical Oncology, Weston, USA (GRID:grid.418628.1) (ISNI:0000 0004 0481 997X)
4 University of Tennessee Health Science Center, Department of Medicine-Hematology, Memphis, USA (GRID:grid.267301.1) (ISNI:0000 0004 0386 9246)