Prognosis of Myelodysplastic Syndromes (MDS)
The prognosis of MDS is highly variable, with median overall survival ranging from a few weeks to several years, and a 5-year survival rate of approximately 37% overall, with risk of progression to acute myeloid leukemia (AML) at 25%-35% at 5 years. 1, 2
Risk Stratification Systems
The prognosis of MDS depends primarily on three key factors:
- Cytogenetic abnormalities
- Bone marrow blast percentage
- Number and severity of cytopenias
International Prognostic Scoring System (IPSS)
The IPSS has been the standard prognostic tool and is used by health agencies for drug approval in MDS 1. It stratifies patients into four risk groups:
- Low
- Intermediate-1
- Intermediate-2
- High
For treatment purposes, these are often grouped as:
- Lower-risk MDS: IPSS low and intermediate-1
- Higher-risk MDS: IPSS intermediate-2 and high
Revised IPSS (IPSS-R)
The IPSS-R provides more refined risk stratification with five groups 1:
- Very low risk
- Low risk
- Intermediate risk
- High risk
- Very high risk
Each risk category has significantly different outcomes for overall survival and risk of progression to AML 1.
WHO Classification-Based Prognostic Scoring System (WPSS)
This system incorporates:
- WHO classification
- Karyotype
- Transfusion dependency
It provides additional prognostic value, particularly for patients in lower IPSS risk groups 1.
Survival Outcomes by Risk Group
- Lower-risk MDS: Median survival of approximately 3-10 years 2
- Higher-risk MDS: Median survival of less than 3 years 2
Genetic Factors Affecting Prognosis
Cytogenetic Abnormalities
Specific cytogenetic abnormalities have significant prognostic implications:
- Good prognosis: Isolated del(5q) in low-risk MDS
- Poor prognosis: Complex karyotype, TP53 mutations 1
Somatic Mutations
Several gene mutations affect prognosis 1:
Poor prognosis mutations:
- TP53
- ASXL1
- RUNX1
- EZH2
- ETV6
- DNMT3A
Better prognosis mutations:
- SF3B1 (when present as an initiating event)
The context of mutations matters significantly - the same mutation may have different prognostic implications depending on:
- Co-occurring mutations
- MDS subtype
- Timing of mutation acquisition
- Treatment received 1
Patient-Related Prognostic Factors
Several patient factors affect prognosis independently of disease characteristics 1:
- Age: Increasing age is an independent adverse prognostic factor
- Performance status: Poor functional status correlates with worse outcomes
- Comorbidities: Presence of significant comorbidities negatively impacts survival
Recent Advances in Prognostication
The Molecular International Prognostic Scoring System (IPSS-M) has shown improved prognostic discrimination compared to IPSS-R, with better prediction of overall survival and leukemia-free survival 3. This system incorporates molecular mutations with clinical parameters.
Causes of Death
Bone marrow failure complications (infection and hemorrhage) are the leading causes of death, with more patients dying from these complications than from progression to AML 1.
Prognostic Pitfalls and Caveats
Mutation context matters: The same mutation may have different prognostic implications depending on co-occurring mutations and disease context 1
Evolving disease: MDS is not static - regular reassessment is necessary as the disease may progress
Treatment impact on prognosis: Some treatments may alter the natural history of specific genetic subtypes (e.g., ASXL1 mutations generally indicate poor prognosis but may be associated with better outcomes during azacitidine treatment) 1
Minimum genetic testing: While comprehensive genetic testing provides the most accurate prognosis, a core set of 15 genes can provide sufficient information for risk stratification 3
Transplant considerations: In patients undergoing hematopoietic stem cell transplantation, molecular features significantly impact post-transplant outcomes and relapse risk 3
By using these prognostic tools and considering both disease and patient-related factors, clinicians can provide more accurate prognostic information and guide appropriate treatment selection for patients with MDS.