The origins of therapy-related myeloid neoplasms

It has been shown that patients treated with cytotoxic chemotherapies are at an increased risk of developing therapy-related myeloid neoplasms. In addition, previous studies have demonstrated that these malignancies are always preceded by clonal hematopoiesis. In this video, Francesco Maura, MD, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, summarizes the findings of a study investigating the mutational processes involved in progression of clonal hematopoiesis to therapy-related myeloid neoplasms. Using whole-genome sequencing (WGS), the study was able to detect when a particular mutation was acquired and define chemotherapy signatures. It was found that all patients exposed to platinum prior to developing a myeloid neoplasm had a platinum mutational signature whilst less than half of the patients exposed to melphalan or who had undergone autologous stem cell transplantation (ASCT) had a melphalan signature. This suggests that in these patients, pre-therapy-related myeloid neoplasm clonal hematopoiesis clones were re-infused during ASCT, thereby avoiding chemotherapy exposure. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.