Improving MDS Risk Assessment: The Role of Monocytopenia and Lymphocytopenia Beyond IPSS-R
Marijana Virijevic1,2, Ljubomir Jakovic1,2, Lazar Trajkovic1
1Clinic of Hematology, University Clinical Center of Serbia, Dr. Koste Todorovica 2, 11000 Belgrade, Serbia.
Abstract:
Background and Objectives: The revised international prognostic scoring system (IPSS-R) remains the most widely used prognostic tool for myelodysplastic syndrome (MDS). There is growing evidence that inflammation and immunological dysregulation are important in the pathogenesis of MDS. Moreover, monocytopenia and lymphocytopenia are correlated with adverse outcomes in patients with MDS. However, standard guideline-driven diagnostic and prognostic models do not evaluate host immunity parameters. This study explored the prognostic relevance of monocytopenia and lymphocytopenia at diagnosis for overall survival (OS) as medical endpoints independent of IPSS-R. Materials and Methods: This retrospective study included 217 patients with MDS diagnosed and treated at the University Clinical Center of Serbia between July 2019 and July 2024. MDS was diagnosed based on the 2016 World Health Organization (WHO) criteria. Results: Univariate analysis revealed that patients with monocytopenia (absolute monocyte count (AMC) < 0.3 × 109/L) had adverse outcomes compared to individuals with normal AMC (AMC ≥ 0.3 × 109/L) (median OS with/without risk factor 20 months vs. 60 months, respectively, log rank test p = 0.0009). Moreover, lymphocytopenia (absolute lymphocyte count (ALC) < 1.2 × 109/L) was shown to have a significant impact on survival (median OS with/without risk factor 17 months vs. 29 months, respectively; log-rank p = 0.0182). In further multivariate analysis, IPSS-R, AMC < 0.3 × 109/L, ALC < 1.2 × 109/L, and DMAs/HSCT were identified as independent prognostic factors for OS (Cox multivariate model, p < 0.001, p = 0.0237, p = 0.006, p < 0.001, respectively). Conclusions: Our findings suggest that ALC and AMC can serve as readily accessible and verifiable prognostic tools in MDS at presentation. Combined with IPSS-R, these markers may provide additional prognostic insights, enabling better risk stratification in MDS patients who could benefit from future immunotherapies.
Insights
Low monocyte and lymphocyte counts predict worse survival in myelodysplastic syndrome (MDS). These immune markers, alongside the IPSS-R score, offer valuable prognostic insights for better patient risk stratification.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- The International Prognostic Scoring System-Revised (IPSS-R) is the standard prognostic tool for MDS.
- Inflammation and immune dysregulation are implicated in MDS pathogenesis, yet standard models lack immune parameters.
Purpose of the Study:
- To investigate the prognostic relevance of monocytopenia and lymphocytopenia at diagnosis for overall survival (OS) in MDS patients.
- To assess whether absolute monocyte count (AMC) and absolute lymphocyte count (ALC) serve as independent prognostic factors beyond the IPSS-R.
Main Methods:
- Retrospective study of 217 MDS patients diagnosed between July 2019 and July 2024.
- MDS diagnosis based on 2016 World Health Organization (WHO) criteria.
- Analysis of overall survival (OS) in relation to AMC (< 0.3 × 10^9/L) and ALC (< 1.2 × 10^9/L) using univariate and multivariate models.
Main Results:
- Monocytopenia (AMC < 0.3 × 10^9/L) was associated with significantly shorter median OS (20 months vs. 60 months, p = 0.0009).
- Lymphocytopenia (ALC < 1.2 × 10^9/L) also significantly impacted survival (median OS 17 months vs. 29 months, p = 0.0182).
- Multivariate analysis identified IPSS-R, low AMC, low ALC, and treatment (DMAs/HSCT) as independent prognostic factors for OS.
Conclusions:
- Absolute monocyte count (AMC) and absolute lymphocyte count (ALC) are accessible and reliable prognostic markers in MDS at diagnosis.
- These immune parameters, when combined with IPSS-R, enhance prognostic accuracy for MDS patients.
- Findings support the use of AMC and ALC for improved risk stratification and may guide future immunotherapies in MDS.
