In this episode, Prof. Robin Foà and Dr. Filippo Milano are joined by Dr. Fred Appelbaum from the Fred Hutchinson Cancer Center to reflect on the persistent challenges and evolving landscape of acute myeloid leukemia (AML). Unlike other hematologic malignancies that have seen major therapeutic revolutions, AML remains bound to the traditional 7+3 regimen, a reminder of how complex its biology truly is.

The conversation delves into the biological roots of AML, emphasizing that the disease originates in the myeloid stem cell—an essential element of hematopoiesis that cannot be eradicated without profound consequences. This fundamental limitation has slowed progress compared with CML, CLL, or ALL, where targeted therapies have reshaped outcomes. Dr. Appelbaum reflects on the need to understand the molecular journey from normal stem cells to leukemic clones, envisioning future treatments capable of selectively eliminating malignant mutations while preserving healthy hematopoiesis.

A major theme of the discussion is the impact of Venetoclax, which has transformed induction therapy for elderly patients, offering higher remission rates and better tolerability. Yet, the question remains whether this improvement translates into cure or simply extends survival. Dr. Milano highlights its role as a bridge to transplant, while both he and Prof. Foà note the growing challenge of Venetoclax resistance and the need for more durable solutions.

The debate then turns to the role of transplantation in intermediate-risk AML. When should patients undergo transplant in first remission (CR1), and how should minimal residual disease (MRD) guide this decision? While studies suggest comparable outcomes between early and delayed transplantation, the practical reality is more nuanced, depending on MRD status, patient age, and access to specialized centers. Prof. Foà voices caution about relying on non-standardized, in-house MRD assays, stressing the ethical and clinical importance of centralized and validated methodologies.

Throughout the discussion, the speakers underscore how scientific progress in AML remains uneven—marked by breakthroughs like Venetoclax but constrained by the disease’s intrinsic biology. As the episode closes, they draw inspiration from the success story of acute promyelocytic leukemia (APL), once one of the deadliest forms of AML and now often cured without chemotherapy or transplant.

This dialogue is a candid examination of both frustration and hope—a reminder that even in areas where progress has lagged, persistent research and collaboration continue to push the boundaries of what is possible in the treatment of AML.