Age-Stratified Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndromes: A Comprehensive Review.

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.