Allogeneic Stem Cell Transplantation: The Relevance of Conditioning Regime Intensity for Myelodysplastic Syndromes (MDS)

Allogeneic hematopoietic cell transplantation (alloHCT) is the sole curative therapy for myelodysplastic syndrome (MDS). While alloHCT clearly confers a significant survival advantage in high-risk MDS, it is less clear how the disease burden and impact of conditioning intensity impact survival. This review addresses critical issues surrounding this topic, emphasizing the unique cell biology of MDS and the evolving concepts of conditioning intensity compared to other diseases, including acute myeloid leukemia (AML). The review is structured around three interconnected themes. First, it clarifies the varying interpretations of conditioning intensity. Second, it examines the interplay between disease burden at transplant and conditioning intensity in determining outcomes, including a comparative analysis with acute myeloid leukemia (AML) to highlight similarities and differences. Third, it explores the relationship between conditioning regimen intensity and immune reconstitution, particularly focusing on the graft-versus-tumor (GvT) effect and its potential modulation by conditioning intensity. Understanding the stem cell target of conditioning regimens is emphasized, as the persistence of the underlying MDS stem cell necessitates a thorough understanding of this concept for improved therapeutic strategies.