In this episode, Prof. Robin Foà and Dr. Filippo Milano look back on twenty-five years of remarkable progress in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Once regarded as one of the most devastating hematologic malignancies, with prognosis considered among the worst in oncology, Ph+ ALL has undergone a dramatic transformation thanks to targeted therapies and innovative treatment strategies.

The conversation traces the pioneering decision to replace intensive chemotherapy with tyrosine kinase inhibitors and steroids, a bold approach that opened the way to higher remission rates and better tolerability, especially for older patients. From the early use of Imatinib to the evolution toward second- and third-generation TKIs, this paradigm shift has steadily improved outcomes and reshaped clinical practice. The discussion also highlights the D-ALBA study, where Dasatinib combined with Blinatumomab marked a new era by eliminating both induction and consolidation chemotherapy while achieving durable survival in the majority of patients.

Foà and Milano explore how minimal residual disease monitoring has become central to guiding therapy and reconsidering the role of transplant, once seen as the only curative option. They also reflect on the challenges that remain, including unequal access to modern therapies and the need for standardized laboratory infrastructures worldwide. While CAR-T cells play an expanding role in other leukemias, their use in Ph+ ALL remains limited in the frontline setting, reinforcing the centrality of TKIs and immunotherapy as the foundation of treatment.

This dialogue is both a scientific journey and a story of hope, showing how determined research, clinical innovation, and international collaboration have turned a disease once defined by despair into one where cure is now a realistic possibility for many patients.