Abstract
Background
Acute myeloid leukemia (AML) shows significant clinical and molecular diversity[1]. The ELN 2022 risk stratification system offers a prognosis basis for primary AML patients but is less effective for elderly and frail individuals[2]. This study uses real-world data to address these limitations by combining baseline characteristics, ELN 2022 risk stratification, and treatment response indicators[3]. It aims to create a weighted prognostic scoring system for a more comprehensive and dynamic AML prognosis and to enhance individualized treatment guidance.
Aim
To create and validate a new, clinically applicable weighted scoring system for survival prediction, based on ELN 2022 risk stratification, incorporating multidimensional prognostic factors like baseline clinical traits, treatment response (including dynamic change indicators), and MRD clearance kinetics.
Methods
This single-center retrospective cohort study analyzed 198 patients with primary AML (dn-AML) treated at Henan Provincial People's Hospital from June 2018 to March 2024. It assessed baseline characteristics, ELN 2022 risk stratification, and treatment responses, using SPSS 22.0 and R/Bioconductor 3.6.1 for data analysis.
Results
The study involved 198 patients with dn-AML (114 males, 57.6%; median age 52.1 years). According to ELN 2022 risk stratification, 38.9% were low-risk (77 patients), 27.8% intermediate-risk (55 patients), and 33.3% high-risk (66 patients). The platelet rate of change (pltv) was calculated as the difference from baseline platelets after the first chemotherapy, resulting in three groups: low (pltv<0, 15.7%, 31 cases), intermediate (pltv 0-5, 38.4%, 76 cases), and high (pltv≥5, 46.0%, 91 cases). No significant differences were found among the groups regarding gender, albumin, induction time point 1 (TP1), age, PT, and CR2 levels. However, the high pltv group had a lower proportion of high-risk ELN patients (23.1% vs. 39.5% vs. 48.4%, p=0.007) and a higher complete remission rate after the first chemotherapy (82.4% vs. 71.1% vs. 35.5%, p<0.001).The MRD conversion rate increased after the second treatment (tp2)(68.1% vs 64.5% vs 41.9%, p=0.025), with significantly higher baseline hemoglobin (≥102 g/L) and platelet (≥20×10⁹/L) levels (93.5% vs 92.1% vs 70.3%, p<0.001; 3.3% vs 28.9% vs 32.3%, p<0.001).
Cox regression analysis identified key independent prognostic factors for overall survival: platelets <20×10⁹/L (HR 2.8, p=0.002), low platelet variability (HR 2.34, p=0.036), albumin <30 g/L (HR 2.57, p=0.02), MRD positive after TP2 (HR 2.45, p=0.002), age >65 years (HR 2.9, p=0.014) and 45-65 years (HR 2.16, p=0.018), and prothrombin time ≥14s (HR 1.79, p=0.032). The ELN 2022 risk stratification was also included (low-risk reference; intermediate-risk HR 1.24, p=0.504; high-risk HR 1.48, p=0.21). These factors were used to create a weighted prognostic scoring system, with AUCs for predicting 1-, 2-, and 3-year survival of 0.729, 0.753, and 0.755, respectively.
Patients were categorized into three groups based on total scores: good (0-4, 43.9%), moderate (5-6, 20.6%), and poor (7-15, 35.6%). Significant differences in 3-year survival rates were observed: 78.3% for good, 59.0% for moderate, and 26.5% for poor (p<0.0001). This new system notably reclassified 14.08% of ELN low-risk and 34% of ELN intermediate-risk patients into the poor prognosis group, enhancing prognostic risk differentiation.
Conclusion
This study developed a novel prognostic scoring system that enhances the current AML assessment by incorporating baseline characteristics, ELN 2022 risk stratification, and key treatment response metrics (platelet change rate, MRD clearance status). The model effectively predicts survival and identifies high-risk patients overlooked by ELN stratification. Future multicenter, large-sample prospective studies are required for external validation and clinical application.
References:
Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377.
Lachowiez CA, Long N, Saultz J, et al. Comparison and validation of the 2022 European LeukemiaNet guidelines in acute myeloid leukemia. Blood Adv. 2023;7(9):1899-1909.
Rausch C, Rothenberg-Thurley M, Dufour A, et al. Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia. 2023;37(6):1234-1244.