FLIPI Calculator
The Follicular Lymphoma International Prognostic Index (FLIPI) is a clinical tool used to predict the survival and prognosis of patients diagnosed with follicular lymphoma (FL). Developed by an international collaborative group in 2004, it replaced older, less specific lymphoma models by identifying five clinical risk factors that specifically influence the outcomes of this common indolent non-Hodgkin lymphoma (Solal-Céligny et al., 2004).
The primary goal of the FLIPI is to help clinicians stratify patients into risk categories, which can guide the timing and intensity of treatment.
The Five Clinical Risk Factors
The index assigns 1 point for each of the following five criteria present at the time of diagnosis. A helpful mnemonic used by clinicians is "NoLASH".
| Factor | Threshold / Definition |
| N (Nodes) | Number of nodal areas $> 4$ |
| L (LDH) | Serum Lactate Dehydrogenase (LDH) above the upper limit of normal |
| A (Age) | Age $\ge 60$ years |
| S (Stage) | Ann Arbor Stage III or IV |
| H (Hemoglobin) | Hemoglobin level $< 12.0$ g/dL |
Risk Stratification and Survival Rates
The total number of points determines the patient's risk group. The original study established the following 5-year and 10-year overall survival (OS) rates based on these scores:
| Risk Group | Points | Distribution | 5-Year Survival | 10-Year Survival |
| Low Risk | 0 – 1 | ~36% | 91% | 71% |
| Intermediate | 2 | ~37% | 78% | 51% |
| High Risk | $\ge 3$ | ~27% | 53% | 36% |
Note: These survival statistics were derived from data before the widespread use of Rituximab. In the modern era of chemo-immunotherapy, survival rates for all categories have significantly improved, though the FLIPI remains a valid tool for relative risk assessment (Federico et al., 2009).
The Evolution: FLIPI-2 and m7-FLIPI
While the original FLIPI remains the most widely used in clinical practice, newer models have been developed to address changing treatments and molecular science:
FLIPI-2
Introduced in 2009, FLIPI-2 focuses on Progression-Free Survival (PFS) rather than overall survival. It uses different variables, including the diameter of the largest lymph node ($> 6$ cm) and $\beta$2-microglobulin levels, reflecting the shift toward long-term disease control in the era of monoclonal antibodies (Federico et al., 2009).
m7-FLIPI
The m7-FLIPI is a "clinicogenetic" index. it combines the clinical factors of the original FLIPI with the mutation status of seven genes (including EZH2, ARID1A, and CARD11). This molecular approach is highly accurate at identifying patients who may experience early treatment failure (Pastore et al., 2015).
Clinical Application
The FLIPI is not intended to dictate whether a patient should start treatment—that decision is usually based on the GELF criteria (symptoms, bulk, and organ function). Instead, the FLIPI helps the physician and patient understand the likely "behavior" of the disease over time, allowing for more informed discussions about prognosis and clinical trial eligibility.
References
- Solal-Céligny, P., et al. (2004). Follicular Lymphoma International Prognostic Index. Blood, 104(9), 1258-1265. https://doi.org/10.1182/blood-2003-12-4434
- Federico, M., et al. (2009). FLIPI2: a new prognostic index for follicular lymphoma developed by the International Follicular Lymphoma Prognostic Factor Project. Journal of Clinical Oncology, 27(27), 4555-4562. https://doi.org/10.1200/JCO.2008.21.3991
- Pastore, A., et al. (2015). Integration of gene mutations in risk stratification of follicular lymphoma: an analysis of the m7-FLIPI. The Lancet Oncology, 16(9), 1111-1122.
- Buske, C., et al. (2006). The Follicular Lymphoma International Prognostic Index (FLIPI) separates patients who benefit from rituximab: results of the GLSG. Blood.
