Ann Lab Med.  2025 Jan;45(1):44-52. 10.3343/alm.2024.0089.

Assessing the Relevance of Non-Molecular Prognostic Systems for Myelodysplastic Syndrome in the Era of Next-Generation Sequencing

• Lincango M
• Andreoli V
• Rivello HG
• Bender A
• Catalán AI
• Rahhal M
• Delamer R
• Asinari M
• Orgueira AM
• Castro MB
• Osorio MJM
• Navickas A
• Grille S
• Agriello E
• Arbelbide J
• Basquiera AL
• Belli CB

• KMID: 2563854
• DOI: http://doi.org/10.3343/alm.2024.0089

Abstract

Background
The Molecular International Prognostic Scoring System (IPSS-M) has improved the prediction of clinical outcomes for myelodysplastic syndromes (MDS). The Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS), based on classical clinical parameters, has outperformed the IPSS, revised version (IPSS-R). For the first time, we validated the IPSS-M and other molecular prognostic models and compared them with the established IPSS-R and AIPSS-MDS models using data from South American patients.
Methods
Molecular and clinical data from 145 patients with MDS and 37 patients with MDS/myeloproliferative neoplasms were retrospectively analyzed.
Results
Prognostic power evaluation revealed that the IPSS-M (Harrell’s concordance [C]-index: 0.75, area under the receiver operating characteristic curve [AUC]: 0.68) predicted overall survival better than the European MDS (EuroMDS; C-index: 0.72, AUC: 0.68) and Munich Leukemia Laboratory (MLL) (C-index: 0.70, AUC: 0.64) models. The IPSS-M prognostic discrimination was similar to that of the AIPSS-MDS model (C-index: 0.74, AUC: 0.66) and outperformed the IPSS-R model (C-index: 0.70, AUC: 0.61). Considering simplified low- and high-risk groups for clinical management, after restratifying from IPSS-R (57% and 32%, respectively, hazard ratio [HR]: 2.8; P = 0.002) to IPSS-M, 12.6% of patients were upstaged, and 5% were downstaged (HR: 2.9; P = 0.001). The AIPSS-MDS recategorized 51% of the low-risk cohort as high-risk, with no patients being downstaged (HR: 5.6; P < 0.001), consistent with most patients requiring disease-modifying therapy.
Conclusions
The IPSS-M and AIPSS-MDS models provide more accurate survival prognoses than the IPSS-R, EuroMDS, and MLL models. The AIPSS-MDS model is a valid option for assessing risks for all patients with MDS, especially in resource-limited centers where molecular testing is not currently a standard clinical practice.

Keyword

Artificial Intelligence Prognostic Scoring System; Model; Molecular International Prognostic Scoring System; Myelodysplastic syndrome; Prognostic; Risk assessment; South America; Survival analysis; Therapy

Figure

• 

  Fig. 1 Clinical assessment of IPSS-R and IPSS-M for 182 patients. (A) Sankey plot for restratification from the IPSS-R to the IPSS-M model using five risk groups. (B) Kaplan–Meier probability estimates of OS across the IPSS-R (top) and IPSS-M (bottom) categories. The dashed gray lines represent the median values. The global P was calculated using the log-rank test. Each HR and associated P were calculated by setting the low-risk group as the reference. Abbreviations: IPSS-R, International Prognostic Scoring System, revised version; IPSS-M, Molecular International Prognostic Scoring System; OS, overall survival; HR, hazard ratio; NE, not evaluable; mo, months.

• 

  Fig. 2 Prognostic power of several models for OS. The prognostic power was assessed based on (A) the AUC or (B) Harrell’s C-index determined with the IPSS-M, IPSS-R, AIPSS-MDS, EuroMDS, and MLL models. In panel B, the red line represents the risk encoded as categories using five risk categories (after merging the moderate-risk groups) for the IPSS-R and IPSS-M models and the quintiles using risk scores obtained from the original training set for the AIPSS-MDS model. The blue line represents a continuous score. Abbreviations: OS, overall survival; AUC, area under the curve; C, concordance; IPSS-M, Molecular International Prognostic Scoring System; IPSS-R, International Prognostic Scoring System, revised version; AIPSS-MDS, Artificial Intelligence Prognostic Scoring System for MDS; EuroMDS, European MDS; MLL, Munich Leukemia Laboratory.

• 

  Fig. 3 Variant distribution, restratification, and OS analysis with different risk models. (A, C) Violin plots showing the number of variants as the risk groups changed when switching from the IPSS-R model to (A) the IPSS-M model or (C) the AIPSS-MDS model, affecting patient therapy. (B) Sankey plot depicting the percentage of patients restratified among the models. (D) Kaplan–Meier probability estimates of the OS for low- and high-risk groups of patients with available survival data. The AIPSS-MDS risk groups were defined based on the median risk score from the original training set by Mosquera, et al. [15]. Risk groups were defined using a risk-score cut-off of 3.5 for IPSS-R and a cut-off of 0 for IPSS-M. Each HR and associated P were calculated by setting the low-risk group as the reference. Abbreviations: OS, overall survival; IPSS-R, International Prognostic Scoring System, revised version; IPSS-M, Molecular International Prognostic Scoring System; AIPSS-MDS, Artificial Intelligence Prognostic Scoring System for MDS; HR, hazard ratio; NA, not available; mo, months.

Reference

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