CNS-IPICNS Relapse Risk Stratification
Clinical & Lab Parameters
High-Risk Nodal/Extranodal Sites
Relapse Risk
Low Risk
0Points
Clinical Strategy
Low estimated CNS relapse risk. CNS prophylaxis is typically not recommended.
Guidelines & Evidence
Verified
Last Review: 2026
When to Use
Clinical Use
All patients with newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL).
To identify patients at high risk (≥ 10% risk) for CNS recurrence.
To guide the decision for prophylactic intrathecal or systemic High-Dose Methotrexate.
How it Works
The 6 Risk Factors (1 Point Each)
Age > 60 years
LDH > Upper Limit of Normal
Ann Arbor Stage III or IV
Extranodal involvement > 1 site
Involvement of kidney or adrenal glands (Specific extranodal site)
Risk Strata
| Score | Risk Group | 2-Year CNS Relapse Risk |
|---|---|---|
| 0 - 1 | Low Risk | 0.6% |
| 2 - 3 | Intermediate Risk | 3.4% |
| 4 - 6 | High Risk | 10.2% |
Clinical Pearls
The Adrenal/Kidney Factor
Involvement of the kidneys or adrenal glands is a powerful independent predictor of CNS relapse. Even if other factors are low, patients with disease in these locations should be considered for high-risk management and baseline CNS staging with LP/Flow Cytometry.
Prophylaxis Controversy
While CNS-IPI identifies high-risk patients, the absolute benefit of intrathecal methotrexate prophylaxis remains debated in the modern R-CHOP era. Many clinicians now favor high-dose systemic methotrexate (HD-MTX) as a more effective alternative for those in the High Risk (4-6) group.
The Evidence
Key Reference
CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP
Schmitz N et al. • Journal of Clinical Oncology. 2016;34(26):3150-6
Last Comprehensive Review: 2026