Allogeneic transplantation and frontline therapy shape survival outcomes in secondary AML: Real-world epidemiology and prognostic insights

Abstract Background: Secondary acute myeloid leukemia (sAML) continues to be associated with poor prognosis. Identification of subgroups with markedly superior outcomes and elucidation of prognostic factors remain vital for optimizing management. Objectives: To characterize epidemiological features, treatment strategies, and survival outcomes (OS, PFS) in sAML, analyzing the impact of allogeneic transplantation, ELN 2017 risk categories, and the existence of a “favorable plus” outlier subgroup with distinct biological features. Methods: A retrospective registry of 143 sAML patients treated at three centres within Institut Català d'Oncologia (ICO Girona, Badalona, Hospitalet) was analyzed. Demographics, disease subtype, front-line therapy, and ELN 2017 risk were captured. OS and PFS were measured from diagnosis. Survival was compared by treatment strategy, ELN risk, and transplant status. The “favorable plus” subgroup was defined as ELN-favorable patients younger than 60 years who achieved OS beyond 36 months. The specific cytogenetics and access to intensive induction and allogeneic transplantation were recorded for this group. Results: Cohort characteristics: Median age 74 (range 27–92), 55% male and 45% female. 94% sAML post-MDS or cytotoxic therapy. ELN 2017 risk: Adverse 51%, intermediate 23%, favorable 13%, favorable plus 3% (n=4), undetermined 13%. Frontline therapy: Intensive induction 3+7 (27%), HMA-based (32%) all venetoclax-azacitidine, palliative/supportive (35%). Transplantation: 13% underwent allogeneic transplantation. Survival: Median OS (global): 4.8 months; median PFS: 3.6 months. By ELN 2017: adverse 4.5 months, intermediate 5.2, favorable 6.7. Favorable plus subgroup (n=4): All patients were younger than 60 years and presented classical ELN-favorable cytogenetics [e.g., inv(16)(p13q22), t(8;21)(q22;q22), and NPM1-mutated/FLT3-ITD negative]. All received intensive induction 3+7 followed by allogeneic transplantation and achieved durable complete remission. In this group, median OS reached 47.1 months and all patient MRD negative pre allogenic transplantation. By treatment: induction 6.8 months, HMA-based 5.1, venetoclax-AZA 7.2, palliative 1.8. By transplantation: TPH median OS 12.4 months vs no TPH 3.2 months (p < 0.000001). Interpretation: The “favorable plus” subgroup demonstrates that, in sAML, younger age, favorable cytogenetics, intensive induction, and consolidative transplantation can yield long-term survival exceeding four years—outcomes not observed in standard-risk or older patients. Conclusions: In this multicenter sAML series, prognosis remains very poor for most patients, yet those younger than 60 years, with ELN-favorable cytogenetics and access to intensive induction plus allogeneic transplant (“favorable plus” subgroup), achieve exceptional long-term survival. These findings reinforce the critical importance of early risk stratification, intensive strategies, and transplant referral for optimal candidates, and highlight the urgent need for advances in other sAML profiles.