. Autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a promising therapeutic strategy for patients with severe and treatment-refractory autoimmune diseases (ADs), offering the potential for sustained remission through profound immune resetting. The objective of this narrative review is to analyze the key principles and clinical considerations guiding the selection of conditioning regimens for AHSCT across various autoimmune indications. A comprehensive literature search was conducted using PubMed, Scopus, and European Society for Blood and Marrow Transplantation (EBMT) registry data, encompassing studies published between 1998 and 2025. The review identifies three intensity tiers of conditioning regimens—low-intensity (non-myeloablative), intermediate-intensity (immunoablative), and high-intensity (myeloablative)—with intermediate-intensity protocols, specifically cyclophosphamide plus anti-thymocyte globulin (Cy-ATG) and BEAM plus ATG (BEAM-ATG), constituting the current standard. Comparative analyses from EBMT registry data reveal comparable efficacy between Cy-ATG and BEAM-ATG in relapsing-remitting multiple sclerosis, while Cy-ATG demonstrates a superior safety profile. Anti-thymocyte globulin is universally employed across conditioning protocols, though significant variability in dosing and administration persists among transplant centers. Disease-specific factors, including disease type, organ function, comorbidities, and center expertise, critically influence regimen individualization. Metabolic and electrolyte disturbances during high-dose cyclophosphamide conditioning necessitate close monitoring. Individualized selection of conditioning regimens, guided by disease biology and patient-specific risk factors, remains essential for optimizing transplant outcomes.

autologous hematopoietic stem cell transplantation, conditioning regimen, autoimmune diseases, cyclophosphamide, anti-thymocyte globulin, BEAM, immune reconstitution.

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