Allo-HSCT in Intermediate-Risk AML: Is It Needed?

The journey to unravelling the complexities of AML treatment, especially in intermediate-risk patients, evolves as novel diagnositcs and therapies are embraced.

The following is a summary of the article “Is allogeneic transplantation necessary in acute myeloid leukaemia of intermediate risk in the first complete remission?” by Marcos Rivada et al (Hospital Clinico Universitario, Valencia, Spain), which is part of the Proceedings of the 4th European Congress controversies in Leukemias, held in Brussels, Belgium, 20-21 November, 2023.

Acute myeloid leukaemia (AML) presents a formidable challenge in the medical landscape, with its heterogeneous nature complicating treatment strategies. In a recent comprehensive examination, the evolving understanding of AML, particularly in the intermediate-risk patient cohort, has shed light on critical considerations for post-remission therapy, notably regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT).

The Landscape of AML Treatment

AML arises from acquired genetic alterations, driving the uncontrolled proliferation of immature hematopoietic precursors. This genetic diversity poses significant challenges, particularly in intermediate-risk patients classified according to European LeukemiaNet (ELN) guidelines. Recent advancements, including the identification of new markers and targeted therapies like FLT3 inhibitors, have refined prognostic stratification and treatment paradigms. However, controversies persist, particularly surrounding the role of allo-HSCT in the post-remission phase.

Navigating Post-Remission Options

Allo-HSCT stands as a cornerstone in AML therapy, especially for patients in first complete remission (CR1) with high relapse risks. Yet, determining its utility in intermediate-risk patients remains uncertain. Studies have highlighted the delicate balance between reducing relapse risk and managing treatment-related mortality (TRM), influencing decisions regarding post-remission therapy.

Evolving Definitions and Classifications

Recent updates in classifications, such as the ELN 2022 guidelines, reflect the dynamic nature of AML assessment, particularly in redefining intermediate-risk categories. However, the transition has prompted scrutiny, with some studies questioning the prognostic efficacy of these updates, underscoring the need for ongoing refinement.

Outcomes and Considerations

Comparative analyses have explored the outcomes of various post-remission strategies, including allo-HSCT, auto-HSCT, and consolidation chemotherapy, in intermediate-risk patients. While some studies advocate for the superiority of allo-HSCT, others suggest nuanced approaches based on molecular risk profiles and minimal residual disease (MRD) status.

The Role of MRD and Molecular Markers

MRD emerges as a critical determinant of post-remission therapy, guiding treatment decisions and conditioning regimens in allo-HSCT. Integrating MRD assessment alongside genetic risk profiles offers a personalised approach to therapy, potentially minimising toxicity while optimising outcomes.

Challenges and Future Directions

Despite strides in understanding AML biology and refining treatment strategies, significant uncertainties persist, particularly regarding the role of allo-HSCT in intermediate-risk patients. Addressing these complexities necessitates prospective clinical trials incorporating updated risk stratification and molecular profiling to tailor therapy effectively.

Conclusion

The journey to unravelling the complexities of AML treatment, especially in intermediate-risk patients, continues to evolve. By embracing advances in molecular diagnostics, refining risk stratification, and exploring innovative therapeutic modalities, the medical community endeavours to optimise outcomes and enhance the quality of life for individuals battling this formidable disease.

For the full text article published by Medicom Medical Publishers, see Rivada M et al. Proceedings of the 4th European Congress Controversies in Leukemia,  Brussels, Belgium, 20-21 November, 2023. https://doi.org/10.55788/f6f2b566