Abstract: Allogeneic stem cell transplantation (alloSCT) remains a potentially curative treatment for patients with hematologic malignancies. Nevertheless, relapse and graft failure continue to be major barriers to long-term success. In these high-risk situations, a second alloSCT may represent the only curative option, although outcomes are frequently compromised by high non-relapse mortality and disease progression. Despite improvements in conditioning regimens, donor availability, and supportive care strategies, clinical results remain suboptimal and underscore the importance of careful patient selection.In this study, we report the 15-year experience of our institution-a national reference center for alloSCT in Spain-in managing patients undergoing a second alloSCT. Our objective is to evaluate relevant clinical and transplant-related factors associated with survival outcomes. Ultimately, we aim to enhance the selection process and contribute to a more personalized approach to 2nd-alloSCT, helping clinicians make better-informed decisions about which patients are most likely to benefit from this high-risk but potentially life-saving procedure.

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