Prognosis of Myelodysplastic Syndromes (MDS)
MDS prognosis is highly variable, ranging from survival of a few weeks to several years, with median overall survival of 15-30 months and a 25-35% risk of progression to acute myeloid leukemia at 5 years, making risk stratification using the IPSS or IPSS-R essential for predicting outcomes and guiding treatment decisions. 1
Overall Survival and Disease Progression
The natural course of MDS demonstrates extreme heterogeneity 1:
- Median overall survival: 15-30 months across all risk categories 1
- Lower-risk MDS (IPSS Low/Intermediate-1): Median survival of 3-10 years, with 5-year survival approximately 68% 2, 3
- Higher-risk MDS (IPSS Intermediate-2/High): Median survival less than 3 years 3
- AML transformation risk: 25-35% at 5 years 1
- Primary cause of death: Bone marrow failure (infection and hemorrhage), with more patients dying before overt AML develops 1
Risk Stratification Systems
International Prognostic Scoring System (IPSS)
All patients with MDS must be risk-stratified according to IPSS, as this remains the reference standard used in clinical trials and for regulatory drug approval. 1
The IPSS incorporates three critical prognostic factors 1, 4:
- Bone marrow blast percentage
- Cytogenetic abnormalities
- Number and severity of cytopenias
Revised IPSS (IPSS-R)
The IPSS-R provides enhanced prognostic precision by stratifying patients into five risk groups (very low, low, intermediate, high, and very high risk) with distinct outcomes 1:
- Five refined cytogenetic risk groups based on large multicenter data 1
- Refined categories for bone marrow blasts and peripheral blood cytopenias 1
- Clear differences in overall survival and AML progression risk across all five groups 1
Recommendation: Use IPSS for treatment decisions based on current evidence, but also stratify according to IPSS-R and WPSS in prospective registries and clinical studies 1
WHO Classification-Based Prognostic Scoring System (WPSS)
The WPSS adds prognostic value beyond IPSS, particularly for lower-risk patients 1:
- Incorporates multilineage dysplasia 1
- Includes severe anemia or transfusion dependency 1
- Accounts for bone marrow fibrosis 1
- Enables more accurate prognosis definition, especially in IPSS Low or Intermediate-1 groups 1
Disease-Related Prognostic Factors
Cytogenetic Abnormalities
Specific cytogenetic patterns are among the most powerful prognostic indicators 1, 4:
- Poor-risk cytogenetics (complex karyotype, chromosome 7 abnormalities): Associated with median survival less than 5 years 2
- Favorable cytogenetics (isolated del(5q), normal karyotype): Better prognosis 1
Bone Marrow and Blood Parameters
- Bone marrow blast percentage: Higher percentages predict worse outcomes 1, 4
- Multilineage dysplasia: Adverse prognostic factor 1
- Transfusion dependency: Identifies patients with median survival less than 5 years when present in the first year of diagnosis 2
- Severe cytopenias: Number and severity independently predict survival 1, 4
Molecular and Genetic Factors
Somatic mutations influence overall survival and disease progression 1:
Most frequent mutations with prognostic impact 1:
- TET2 (15-25%)
- SF3B1 (15-30%)
- ASXL1 (10-20%)
- SRSF2 (10-15%)
- RUNX1 (10-15%)
- DNMT3a (10%)
- U2AF1 (5-10%)
- TP53 (5-10%)
- IDH1/2 (5-10%)
- NRAS/KRAS (10%)
Important caveat: While molecular profiling may improve risk stratification, data on independent prognostic impact are still insufficient to recommend routine use in clinical practice 1. However, this is likely to become standard as massive genotyping methods become more accessible 1
Flow Cytometry
Flow cytometry immunophenotyping provides additive prognostic value to reference scoring systems 1:
- Not recommended routinely at present 1
- Can be useful for identifying patient subsets with distinct clinical course and treatment response 1
Patient-Related Prognostic Factors
Age
- Increasing age is an independent adverse prognostic factor 1
- Median age at diagnosis: Approximately 70 years 3
- Age-adjusted survival estimates are provided in various prognostic scoring systems 1
Performance Status and Comorbidities
- ECOG performance status: Relevant for establishing prognosis and treatment choice, particularly in lower-risk MDS 1
- Comorbidities (especially cardiovascular disease): Independent prognostic factors that reduce overall survival 2
- High prevalence of comorbid diseases reported in MDS patients 1
Additional Disease-Related Factors
- Serum markers: LDH, ferritin, and β2-microglobulin levels 1
- Bone marrow fibrosis: Adverse prognostic indicator 1
Treatment Impact on Prognosis
Curative Therapy
Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment and should be considered for higher-risk patients at diagnosis 3, 5:
Disease-Modifying Therapy
Hypomethylating agents (azacitidine, decitabine) are first-line therapy for higher-risk MDS 3:
- Impact disease evolution 1
- Prognostic factors may differ in patients treated with these agents compared to supportive care alone 1
Lower-Risk MDS Therapy
Erythropoiesis-stimulating agents for lower-risk MDS with anemia 3:
- Improve anemia in 15-40% of patients 3
- Median response duration: 8-23 months 3
- Response rates of 40-60% in appropriate patients 2
Clinical Pitfalls and Caveats
Chronological vs. biological age: Chronological age may differ from functional age; consider additional factors when evaluating eligibility for disease-modifying treatments 1
Therapy-related MDS: Has distinct prognostic features and may require separate risk models 6
Dynamic risk assessment: Most prognostic factors were established in cohorts receiving supportive care; factors predicting outcome with newer treatments are still being defined 1
Avoid relying solely on morphology: Cytogenetic analysis is mandatory, particularly for entities like del(5q) MDS 1
AML threshold: The distinction between MDS and AML at 20% blasts (WHO criteria) versus 30% blasts (FAB criteria) affects classification and prognosis 1