FLIPI-2 Calculator for Follicular Lymphoma
FLIPI-2 Calculator for Follicular Lymphoma
FLIPI-2 keeps age and haemoglobin, swaps LDH for beta-2 microglobulin and the nodal count for the largest node’s diameter, and adds marrow involvement. Built on prospectively collected rituximab-era data, and it predicts progression-free survival rather than overall survival.
FLIPI-2 (Federico 2009)
5 factors → 0–5Beta-2 microglobulin 3.4 mg/L against a laboratory upper limit of 2.4 (1); largest involved node 4.1 cm (0); bone marrow involved (1); haemoglobin 13.0 g/dL (0); age 54 (0)
The five factors, and the disagreement about what they are
One point each; range 0 to 5
Low 0 · intermediate 1–2 · high 3–5
- a SOURCE DISAGREEMENT, printed rather than reconciled
- a 2025 review read for this page gives the FLIPI-2 factor set two different ways in one document. Its abstract and summary give the five factors as above; its own body text instead describes FLIPI-2 as FLIPI-1 with LDH simply replaced by beta-2 microglobulin, keeping the nodal-area count and the Ann Arbor stage and omitting the marrow and the node diameter. The review itself flags the inconsistency. This page implements the set above, which is what a clinical-trial protocol appendix lodged on clinicaltrials.gov prints and what that review’s own abstract prints, and the other reading is recorded here rather than quietly dropped
- all five weights are 1
- a count of adverse factors, as in FLIPI-1. The low-risk group is narrower, though: FLIPI-2 low risk is a score of zero, where FLIPI-1 low risk is zero or one
- the endpoint changed
- FLIPI-1 was fitted to overall survival. FLIPI-2 was fitted to PROGRESSION-FREE survival, because in a rituximab-era cohort followed for a few years too few patients die for overall survival to be modelled. The two indices therefore answer different questions and their percentages are not comparable
- the marrow item is the practical limit
- FLIPI-2 cannot be computed without a trephine biopsy, and PET-CT staging has made bone marrow biopsy optional in much of routine practice. An unscored marrow is not a negative marrow
- the cohort and its era
- developed by the International Follicular Lymphoma Prognostic Factor Project on PROSPECTIVELY collected data, in deliberate contrast to FLIPI-1’s retrospective archive series of patients diagnosed between 1985 and 1992. The enrolment years and the exact size of the FLIPI-2 derivation cohort could not be read in any source available for this page and are therefore not stated here. An independent Italian validation in 498 patients diagnosed between 1980 and 2008 reported five-year overall survival of 79% and five-year progression-free survival of 60% overall, with median progression-free survival not reached in the low-risk group, 6.8 years in the intermediate group and 2.1 years in the high-risk group
- what a median is
- a median is the middle of the derivation cohort and not a forecast: half of that cohort reached the figure and half did not, and a figure measured in a cohort treated decades ago is a historical measurement rather than an expectation
Worked example
Beta-2 microglobulin 3.4 mg/L against a laboratory upper limit of 2.4 (1); largest involved node 4.1 cm (0); bone marrow involved (1); haemoglobin 13.0 g/dL (0); age 54 (0)
1 + 0 + 1 + 0 + 0 = 2 adverse factors
2 sits in the 1–2 intermediate-risk band, with three-year progression-free survival of 69% in the derivation data
Drop the marrow involvement and the total is 1 — still intermediate, because FLIPI-2's intermediate band is two points wide. Drop the beta-2 microglobulin as well and the total is 0, which is the ONLY score in the low-risk group
That asymmetry is worth noticing: FLIPI-2 low risk is a score of zero, where FLIPI-1 low risk is zero or one. The same patient can be FLIPI-1 low risk and FLIPI-2 intermediate risk without any disagreement between the two instruments
Check the creatinine before accepting the beta-2 microglobulin point. The analyte is cleared by the kidney, so a reduced glomerular filtration rate raises it independently of the lymphoma — the commonest way this item is scored positive for the wrong reason
FLIPI-1 and FLIPI-2 side by side
| FLIPI-1 | FLIPI-2 | |
|---|---|---|
| Age | Over 60 | Over 60 |
| Haemoglobin | Under 12 g/dL | Under 12 g/dL |
| Tumour-turnover marker | LDH above the ULN | Beta-2 microglobulin above the ULN |
| Disease extent | More than 4 nodal areas | Largest involved node over 6 cm |
| Stage / marrow | Ann Arbor stage III–IV | Bone marrow involvement |
| Low risk | 0 or 1 factor | 0 factors only |
| Intermediate risk | 2 factors | 1 or 2 factors |
| High risk | 3 or more factors | 3 or more factors |
| Endpoint modelled | Overall survival | Progression-free survival |
| Data | Retrospective archive, diagnosed 1985–1992 | Prospectively collected, rituximab era |
The three strata and what they predicted
| Risk group | Adverse factors | 3-year progression-free survival |
|---|---|---|
| Low | 0 | 91% |
| Intermediate | 1 – 2 | 69% |
| High | 3 – 5 | 51% |
Why a second FLIPI exists, and the two items that decide whether it applies
FLIPI-2 is not a correction of FLIPI-1. It is a different instrument, fitted to a different endpoint in a different kind of dataset, and the reason it exists is rituximab. FLIPI-1 was built on retrospectively collected archive records of patients diagnosed between 1985 and 1992 and modelled overall survival. By the mid-2000s that was no longer answerable in a contemporary cohort over a few years of follow-up, because too few patients were dying; so the International Follicular Lymphoma Prognostic Factor Project collected data PROSPECTIVELY and modelled progression-free survival instead.
The factor set changed with it. Age over 60 and haemoglobin under 12 g/dL carried over unchanged. LDH was replaced by beta-2 microglobulin, which performed better as a marker of tumour burden in the new data. The count of nodal areas — the item assessors disagreed on most — was replaced by a single reproducible measurement, the longest diameter of the largest involved node, with a 6 cm threshold. And bone marrow involvement was added. The strata were recut too, and in a way that catches people out: FLIPI-2’s low-risk group is a score of zero alone, where FLIPI-1’s is zero or one. A patient scoring 1 is low risk on FLIPI-1 and intermediate on FLIPI-2, with no disagreement between the instruments at all.
Two items decide whether the index can be computed honestly. The first is the marrow. FLIPI-2 needs a trephine biopsy, and PET-CT staging has made marrow biopsy optional in much of routine follicular lymphoma practice; a marrow that was never taken is not a marrow that was clear, and scoring it zero biases the total towards a better stratum. The second is beta-2 microglobulin, which is cleared by the kidney. Any reduction in glomerular filtration rate raises it, as does any other B-cell malignancy and a good deal of inflammation, so the item is scored positive for non-lymphoma reasons more often than LDH ever was. Read it with the creatinine beside it.
One source read for this page gives the FLIPI-2 factor set two different ways in the same document, and the disagreement is printed above rather than reconciled silently. Every outcome figure here describes the cohort the index was derived in and not the patient in front of you; the spread within one stratum is wider than the gap between strata. Every laboratory threshold here is method- and laboratory-dependent, so the reader’s own laboratory’s reference interval takes precedence. A risk stratum is not a diagnosis and not a plan. This page computes the index, names the stratum and reports what it predicted in the derivation cohort; what follows is a decision for the treating team with the patient.
Frequently asked questions
What are the five FLIPI-2 factors?
Beta-2 microglobulin above the laboratory upper limit of normal, longest diameter of the largest involved node over 6 cm, bone marrow involvement, haemoglobin under 12 g/dL and age over 60 years. One point each. Low risk is a score of 0, intermediate 1 to 2, high 3 or more.
Should I use FLIPI-1 or FLIPI-2?
They answer different questions, so the honest answer is to say which you used. FLIPI-1 predicts overall survival and needs no beta-2 microglobulin and no marrow biopsy, which makes it computable in almost every patient. FLIPI-2 predicts progression-free survival on rituximab-era data and needs both. Most trials still report FLIPI-1, which is the practical argument for computing it as well.
Can I compute FLIPI-2 without a bone marrow biopsy?
No, not faithfully. One of the five items is marrow involvement, and treating an unperformed biopsy as a negative one shifts the score down and can move the patient a whole stratum. If no marrow was taken, record the FLIPI-2 as incomplete.
Why beta-2 microglobulin instead of LDH?
It discriminated better in the prospectively collected dataset FLIPI-2 was fitted to. The trade-off is specificity: beta-2 microglobulin is renally cleared, so impaired kidney function raises it independently of the lymphoma, and it is also raised in other B-cell malignancies and in inflammation.
Do FLIPI-1 and FLIPI-2 give the same risk group?
Often, but not always, and a mismatch is not an error. Only two of the five factors are shared, the low-risk definitions differ — 0 or 1 for FLIPI-1, 0 only for FLIPI-2 — and the modelled endpoints are different. A report quoting “FLIPI intermediate risk” without saying which index it means has left out the important part.
Related calculators
References
- Federico M, et al. Follicular Lymphoma International Prognostic Index 2 (FLIPI-2), from the International Follicular Lymphoma Prognostic Factor Project. J Clin Oncol. 2009. The derivation paper; PROSPECTIVELY collected data, unlike FLIPI’s retrospective archive series.
- Protocol for NCT01234766, Appendix B: FLIPI and FLIPI-2 — both instruments’ items, risk groups and outcome figures. clinicaltrials.gov.
- Prognostic models in follicular lymphoma. Diagnostics (MDPI), 2025 — FLIPI as a pre-rituximab instrument, this review’s own internal disagreement about the FLIPI-2 factor set, and the Arcaini FLIPI-2 validation in 498 patients diagnosed 1980–2008.
- Solal-Céligny P, et al. Follicular Lymphoma International Prognostic Index (FLIPI). Blood. 2004. The derivation paper: a training series of 1,795 patients diagnosed 1985–1992 from retrospective archive data.
- Prognostic indices in follicular lymphoma: the IPI, the Italian Lymphoma Intergroup index and the FLIPI. Hematology Reviews — the training series (1,795 of 5,120 collected, diagnosed 1985–1992), the 36/37/27% distribution and survival by group.
Not medical advice. For healthcare professionals and education. Reference intervals vary by laboratory and assay — always use your own laboratory's. Never base a dose or a treatment decision on this page alone. Full disclaimer at calcengines.com/disclaimer/