Development and validation of a prognostic model for adult patients with acute myeloid leukaemia

EBioMedicine. 2020 Dec:62:103126. doi: 10.1016/j.ebiom.2020.103126. Epub 2020 Nov 22.

Abstract

Background: The high heterogeneity of acute myeloid leukaemia (AML) reflected in the patient- and disease-related factors accounts for the unsatisfactory prognosis despite the introduction of novel therapeutic approaches and drugs in recent years.

Methods: In the development set (n = 412), parameters including age, hematopoietic cell transplantation-comorbidity index, white blood cell count, hemoglobin, biallelic CEBPA mutations, DNMT3A mutations, FLT3-ITD/NPM1 status, and ELN cytogenetic risk status were identified as independent prognostic factors for overall survival (OS) in the multivariable Cox regression analysis. A nomogram combining these predictors for individual risk estimation was established thereby.

Findings: The prognostic model demonstrated promising performance in the development cohort. The calibration plot, C-index (0.74), along with the 1-, 2- and 3-year area under the receiver operating characteristic curve (AUC, 0.76, 0.79, and 0.74, respectively) in the validation set (n = 238) substantiated the robustness of the model. In addition to stratifying young (age ≤ 60 years) and elderly patients (age > 60 years) into three and two risk groups with significant distinct outcomes, the prognostic model succeeded in distinguishing eligible candidates for hematopoietic stem cell transplantation.

Interpretation: The prognostic model is capable of survival prediction, risk stratification and helping with therapeutic decision-making with the use of easily acquired variables in daily clinical routine.

Funding: This work was supported in part by grants from the National Natural Science Foundation of China (81770141), the National Key R&D Program of China (2016YFE0202800), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161406).

Keywords: Acute myeloid leukaemia; Nomogram; Prognostic model; Risk stratification.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Clinical Decision-Making
  • Disease Management
  • Disease Susceptibility
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Mutation
  • Nucleophosmin
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • NPM1 protein, human
  • Nucleophosmin