Age and Genetics Influence Outcomes in Acute Myeloid Leukemia Patients: CETLAM Study

Patient age and genetic risk significantly influence remission and survival outcomes in acute myeloid leukemia (AML), a recent study has reported.

Published in Blood Cancer Journal(Nature Publishing Group, 2025), the multicenter study by the Spanish CETLAM Group evaluated 1,034 adults aged 18–70 years with newly diagnosed AML who were deemed fit for intensive chemotherapy. Conducted between 2012 and 2022 across 15 hospitals, the prospective AML-12 protocol (ClinicalTrials.gov: NCT04687098) assessed real-world outcomes following a uniform regimen of induction cytarabine/idarubicin, high-dose cytarabine (HDAC) consolidation, and allogeneic hematopoietic cell transplantation (alloHCT) where indicated.

Key Outcomes of the study include:

Remission and survival rates differed significantly by age group:

• Complete remission (CR) rate: 77% overall; 79% in patients ≤60 years vs. 73% in those >60 (p = 0.03).
• 4-year overall survival (OS): 53% in younger vs. 33% in older patients (p < 0.001).
• Event-free survival (EFS): 44% vs. 29%; induction mortality: 8% vs. 15% in younger and older patients, respectively.

Genetic risk stratification per ELN-2022 was a key predictor of outcome:

• Patients with favorable profiles (e.g., biallelic CEBPA or NPM1mut/FLT3low) had excellent outcomes, with 4-year OS up to 86%.
• Adverse-risk patients (e.g., TP53 mutations, complex/monosomal karyotype, MECOM rearrangements) showed poor results, with 4-year OS of 14% and EFS of 12%.
• AlloHCT feasibility was lowest in this high-risk group, with only 14% of MECOMr patients undergoing transplant in CR1.

A novel prognostic model—Intensive Chemotherapy Score for AML (ICSA)—was developed and validated:

• Based on age, ECOG, renal and hepatic function, leukocyte counts, and genetic category.
• Stratified patients into six risk tiers with distinct 4-year OS outcomes: 85% (very low risk) to 0% (very high risk).
• Validated in an external cohort (n=581; C-index = 0.71).

This study emphasizes that not all fit AML patients benefit equally from intensive regimens. The integration of molecular risk and clinical parameters via the ICSA score offers a practical, evidence-based tool for oncologists and hematologists to refine treatment strategies. Further, high-risk older patients may require early consideration of alternative or investigational therapies over standard intensive chemotherapy.

Reference:Oñate G, Garrido A, Arnan M, et al. Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group. Blood Cancer Journal (Nature Publishing Group). 2025;15:4. https://doi.org/10.1038/s41408-024-01205-5