Age-Stratified Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With...

Myelodysplastic syndromes (MDS) are clonal disorders with high risk of progression to acute myeloid leukemia (AML). Allogeneic haematopoietic stem cell transplantation (allo-HSCT), including haploidentical HSCT (haplo-HSCT), is the only curative option. Age-stratified selection of conditioning regimens based on organ reserve and comorbidity burdens has been routine clinical practice for many years. However, recent developments warrant a critical re-examination: the incorporation of hypomethylating agents and targeted therapies (decitabine, venetoclax), the introduction of the quantitative Transplant Conditioning Intensity (TCI) score, and emerging data in patients aged ≥ 70 years. This review summarizes age-stratified regimens: myeloablative (MAC), reduced-intensity (RIC), and reduced-toxicity (RTC). In younger patients (< 50 years), MAC achieves 3-year overall survival (OS) > 70% and non-relapse mortality (NRM) < 15%. In middle-aged (50-60 years) and elderly (> 60 years) patients, RIC/RTC yield OS of 60%-70% with NRM < 20%, though these estimates derive largely from retrospective or single-center studies. Adding targeted/hypomethylating agents (e.g., decitabine, venetoclax) has shown promise in reducing relapse in high-risk patients. Age-stratified conditioning combined with these agents forms the core of individualized transplant strategies, reducing NRM and improving efficacy. Prospective, MDS-specific randomized trials are urgently needed to transform these preliminary observations into evidence-based standards.