| Summary: | About 10% of newly diagnosed and 20–30% of therapy-related acute myeloid leukemia (AML) harbors a <i>TP53</i> mutation (<i>mTP53</i>-AML). Unfortunately, this biological subset predicts one of the worst prognoses among patients with AML, specifically a median overall survival of about 7 months with fewer than 10% of patients eventually cured of disease. Although remission rates appear to be increased with venetoclax-based, less-intensive regimens when compared with contemporary, intensive chemotherapy (55–65% vs. 40%), survival appears to be no different between the two approaches. Attempts to discern whether or not the prognosis of <i>mTP53</i>-AML is universally poor have centered around the study of concurrent cytogenetic risk and predicted <i>TP53</i> allelic state, measurable residual disease status and the impact of conditioning intensity for patients proceeding to allogeneic hematopoietic stem cell transplantation. We discuss these considerations in this review and offer the current treatment approach to <i>TP53</i>-mutated AML.
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