How is the International Extranodal Lymphoma Study Group (IELSG) prognostic score calculated for primary central nervous system lymphoma (PCNSL) and how does it guide treatment decisions?

IELSG Prognostic Score for PCNSL

The IELSG prognostic score assigns 1 point for each of five adverse factors: age >60 years, ECOG performance status >1, elevated serum LDH, elevated CSF protein concentration, and involvement of deep brain structures (periventricular regions, basal ganglia, brainstem, or cerebellum), with scores of 0-1,2-3, and 4-5 defining low-, intermediate-, and high-risk groups that predict significantly different 2-year overall survival rates of 80%, 48%, and 15%, respectively 1.

Score Calculation

The IELSG score is calculated by summing five binary variables, each assigned 0 (favorable) or 1 (unfavorable):

• Age: >60 years = 1 point
• Performance Status: ECOG >1 = 1 point
• Serum LDH: Elevated above normal = 1 point
• CSF Protein: Elevated concentration = 1 point
• Deep Brain Involvement: Periventricular regions, basal ganglia, brainstem, and/or cerebellum = 1 point

Risk Stratification

The total score (0-5) stratifies patients into three prognostic groups:

• Low risk (0-1 points): 2-year OS 80% ± 8%
• Intermediate risk (2-3 points): 2-year OS 48% ± 7%
• High risk (4-5 points): 2-year OS 15% ± 7%

This stratification was validated in patients receiving high-dose methotrexate-based chemotherapy, with 2-year OS rates of 85%, 57%, and 24% for the three risk groups, respectively 1.

Clinical Application and Treatment Guidance

While the 2024 EHA-ESMO guidelines 2 emphasize that treatment stratification should be based on age, performance status, organ function, comorbidities, and frailty rather than age alone, the IELSG score provides objective risk assessment that can inform treatment intensity decisions:

For fit patients (age ≤65 years with ECOG PS 0-3, or age ≤70 years with ECOG PS ≤2):

• MATRix regimen (HD-MTX + HD-cytarabine + rituximab + thiotepa) is recommended for induction, achieving 7-year OS of 56% and 7-year PFS of 52% 2
• Consolidation with HDC-ASCT or reduced-dose WBRT based on response and patient factors
• Patients receiving MATRix followed by consolidation achieved 7-year OS of 70% 2

For elderly or less fit patients:

• Less intensive HD-MTX-based regimens (e.g., R-MPV, MTeR) are appropriate
• Treatment decisions must account for renal function (creatinine clearance >50 ml/min), hepatic function, and cardiac function (LVEF >45%) required for HD-MTX 2

Important Caveats

Validation concerns: Some studies have questioned the IELSG score's discriminatory ability. One Norwegian study found the six-tiered IELSG scores required dichotomization into <2 versus ≥2 to have prognostic value, while the three-tiered MSKCC score performed better 3. A Chinese study proposed modifications including age ≥54 years (rather than >60) and LDH/ULN >0.75 (rather than simply elevated) to improve discrimination 4.

Clinical context: The IELSG score was developed in 2003 1 before modern intensive regimens became standard. While it remains useful for risk stratification, treatment decisions should prioritize functional status, organ function, and treatment tolerance over score alone 2. All patients should be evaluated by a multidisciplinary team at specialist centers, and clinical trial enrollment should be prioritized 2.

Deep brain structure involvement is particularly important—this factor independently predicts worse survival and is incorporated into treatment algorithms 1, 3.

The score does not replace comprehensive assessment but provides a validated framework for discussing prognosis and treatment intensity with patients, particularly when considering aggressive consolidation strategies like HDC-ASCT versus less intensive approaches.