How do you determine if a patient with myelodysplastic syndrome (MDS) is at high or low risk?

Risk Stratification in Myelodysplastic Syndrome

Use the Revised International Prognostic Scoring System (IPSS-R) to determine if your MDS patient is high or low risk, as it provides superior prognostic accuracy compared to the original IPSS and stratifies patients into five distinct risk categories based on bone marrow blasts, cytogenetics, and depth of cytopenias. 1

Primary Risk Stratification Tool: IPSS-R

The IPSS-R is the preferred risk stratification system and categorizes patients into five risk groups 1, 2:

• Very Low Risk: Median survival 90 months 1
• Low Risk: Median survival 54 months 1
• Intermediate Risk: Median survival 34 months 1
• High Risk: Median survival 21 months 1
• Very High Risk: Median survival 13 months 1

Three Core Components to Calculate IPSS-R

1. Bone Marrow Blast Percentage 1, 2

• ≤2% blasts

• 2% to <5% blasts

• 5-10% blasts

• 10% blasts

2. Cytogenetic Risk Categories (5 groups instead of original 3) 1, 2

• Very good
• Good
• Intermediate
• Poor
• Very poor

The IPSS-R identifies 16 specific cytogenetic abnormalities versus the previous 6, providing more granular prognostic information 1.

3. Depth of Cytopenias 1, 2

• Hemoglobin levels with specific cutoffs
• Platelet counts with specific cutoffs
• Absolute neutrophil counts with specific cutoffs

Simplified Clinical Approach: Higher vs Lower Risk

For practical clinical decision-making, divide patients into two major categories 1:

Higher-Risk MDS (IPSS Intermediate-2 or High; IPSS-R Intermediate, High, or Very High)

• Bone marrow blasts ≥5% 1
• Poor-risk cytogenetics 1, 3
• Multiple cytopenias 1
• Median survival <2 years without aggressive therapy 1
• High risk of AML transformation 1, 3

Lower-Risk MDS (IPSS Low or Intermediate-1; IPSS-R Very Low or Low)

• Bone marrow blasts <5% 1
• Favorable or intermediate cytogenetics 1, 3
• Median survival 3-10 years 3, 4
• 5-year survival approximately 68% 3, 4

Additional Prognostic Factors Beyond IPSS-R

While not part of the core IPSS-R calculation, these factors provide additional prognostic information 1, 3:

Patient-Related Factors:

• Age (more significant in lower-risk groups) 1, 3
• Performance status 1, 3
• Comorbidities, especially cardiovascular disease 3, 4

Laboratory Markers:

• Serum ferritin 1
• Lactate dehydrogenase 1
• β2-microglobulin 1

Disease Characteristics:

• Transfusion dependency (particularly RBC transfusions) 4, 5, 6
• Multilineage dysplasia 1, 5

Identifying "Lower-Risk" Patients at Risk for Rapid Progression

Critical warning signs in patients classified as lower-risk who may have poor outcomes 5, 6:

• Bone marrow blasts 5-9% (even within "lower risk" category) 6
• Severe cytopenias (hemoglobin, platelets, neutrophils at lower thresholds) 5, 6
• RBC transfusion dependency 5, 6
• Age >60 years 5, 6
• High serum ferritin 5
• Bone marrow fibrosis 5

These patients may require more aggressive monitoring or earlier intervention despite their "lower-risk" classification 5, 6.

Practical Implementation

Online calculators and smartphone apps are available for IPSS-R calculation (http://advanced.ipss-r.com), which simplifies the complex cytogenetic component 1. The IPSS-R has been validated in multiple retrospective studies demonstrating superior risk stratification compared to IPSS, WPSS, and other scoring systems 1.

Treatment Implications Based on Risk

Higher-Risk Disease:

• Hypomethylating agents (azacitidine, decitabine) show survival benefit 1, 3
• Allogeneic stem cell transplantation significantly improves survival (median 40 months for high-risk, 31 months for very high-risk vs. 19 and 12 months without transplant, respectively) 1, 3

Lower-Risk Disease:

• Supportive care with growth factors 3, 4
• Erythropoiesis-stimulating agents for anemia 4
• Iron chelation for transfusion-dependent patients 3

The IPSS-R better identifies which patients benefit from specific therapies, particularly hypomethylating agents and transplantation 1.