Hematology Pills

• Acute Myeloid Leukemia: Progress, Plateau, and the Path Ahead – A Dialogue Between Prof. Robin Foà, Dr. Filippo Milano and Dr. Fred Appelbaum

  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.

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• Ph-Positive Acute Lymphoblastic Leukemia, 25 Years of Progress – A Dialogue Between Prof. Robin Foà and Dr. Filippo Milano

  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.

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• Evolving Strategies in ALL: CAR-T Cells, MRD, and the Decline of Transplant – A Dialogue Between Prof. Robin Foà and Dr. Filippo Milano

  In this episode, we delve into the evolving landscape of Acute Lymphoblastic Leukemia (ALL) treatment, with a focus on cutting-edge therapies and their impact on patient outcomes. We explore the rapid integration of CAR T-cell therapy, now being used earlier in treatment and its effects on survival rates. The discussion also addresses the shifting role of allogeneic transplantation, particularly in light of the economic and clinical advantages of newer therapies. We highlight the importance of minimal residual disease (MRD) monitoring and its ability to guide treatment decisions, potentially sparing patients from invasive procedures. Additionally, we examine the transformative effects of immunotherapies like blinatumomab and inotuzumab, and their role in reducing the reliance on traditional chemotherapy and transplantation. As the field continues to evolve, we consider the future of ALL treatment, including the challenges posed by economic constraints and the move toward personalized medicine.Tune in for an in-depth analysis of these groundbreaking advances in ALL therapy and their potential to redefine treatment paradigms.

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• Transplant as Immunotherapy: The PTCy Revolution, GVHD Control, and the New Era of Allogeneic SCT – A Dialogue Between Prof. Robin Foà and Dr. Filippo Milano

  In this episode, we delve into the transformative changes in allogeneic stem cell transplantation (SCT), a treatment once seen as a last resort for patients but now experiencing a renaissance. Despite the rise of therapies like immunotherapy and CAR-T cells, SCT continues to evolve and remains crucial, particularly with recent breakthroughs. A key focus of the discussion is the introduction of post-transplant cyclophosphamide (PTCy), a groundbreaking advancement in SCT that significantly reduces the incidence of graft-versus-host disease (GVHD), a major complication. PTCy has shown extremely low rates of both acute and chronic GVHD in randomized clinical trials, a major shift from traditional immunosuppressive therapies. While concerns were raised about the potential for increased relapse due to the elimination of reactive T-cells, studies have shown no evidence of an increased relapse risk, making PTCy a game changer.The use of PTCy has also expanded the donor pool, enabling the use of alternative donors such as mismatched relatives and haploidentical donors, which was unthinkable just five years ago. This expansion addresses the global challenge of finding compatible donors, especially for patients from underrepresented ethnic backgrounds or regions with poorly organized donor registries. Additionally, SCT is now being reconsidered as a first-line treatment for several hematologic conditions, thanks to reduced toxicity and the possibility of minimizing pre-transplant chemotherapy. This has also made SCT an option for patients over 75, although careful cardiological evaluation is essential due to potential heart risks associated with cyclophosphamide.Despite the rise of novel therapies, SCT remains a cornerstone in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly for older patients. With advancements in post-transplant care and a better understanding of the microbiome’s influence, SCT will continue to play a pivotal role in treating these diseases. Listen to learn more about how SCT is evolving, maintaining its relevance, and offering hope to patients worldwide.

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• Understanding CAR-T Resistance: Biology, Persistence, and the Pathways to Failure – A Dialogue Between Prof. Robin Foà, Dr. Filippo Milano, and Dr. Marco Ruella

  In this episode of Hematology Pills, Dr. Marco Ruella, Prof. Robin Foà, and Dr. Filippo Milano dive into the challenges of CAR T-cell therapy resistance. They explore key resistance mechanisms, including T-cell dysfunction, the tumor microenvironment, and antigen loss, such as CD19 in relapsed ALL. Dr. Ruella discusses promising strategies to overcome these hurdles, like dual-targeting approaches, and highlights the importance of improving CAR T-cell product quality and monitoring in clinical settings. The episode also touches on the inflammatory side effects, like cytokine release syndrome (CRS) and neurotoxicity (ICANS), and their potential for enhancing the anti-tumor effect. Tune in for a deep dive into the future of CAR T-cell therapies and their evolving role in cancer treatment.

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