GAMMA: A genetic-clinical prognostic model for risk stratification in patients with relapsed/refractory acute myeloid leukemia receiving allogeneic hematopoietic stem cell transplantation.

The prognosis of patients diagnosed with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy. An integrated model incorporating both genetic and clinical features to inform clinical decision-making in the HSCT setting for R/R AML patients is still lacking. In the current study, 301 R/R AML patients who underwent allo-HSCT at Peking University People's Hospital from 2018 to 2023 were included in the derivation group. A total of 297 R/R AML patients from 11 other HSCT centers in China were included in the external validation group. A total of 54 R/R AML patients who underwent allo-HSCT at Peking University People's Hospital in 2025 were assembled as a prospective validation cohort. A comprehensive prognostic model combining clinical factors and genetic abnormalities, including disease status before HSCT, patient and donor age, FLT3-ITD, TP53 mutation, KMT2A rearrangement (KMT2Ar) and complex karyotypes, for R/R AML patients treated with allo-HSCT was developed. Patients were stratified into four risk groups: low-risk, intermediate-low-risk, intermediate-high-risk, and high-risk. In the internal validation cohort, the 1-, 2- and 3-year time-dependent area under the curve (AUC) values of overall survival (OS) were 0.768, 0.795 and 0.799, respectively. In the external validation cohort, the 1-, 2- and 3-year time-dependent AUC values of OS were 0.676, 0.729 and 0.786, respectively. The 1-year AUC of the prospective validation cohort reached 0.79. This model could refine risk stratification in R/R AML patients undergoing allo-HSCT, and potentially inform combination therapy strategies and post-transplantation monitoring.