CLL-IPI: how the chronic lymphocytic leukemia prognostic index is scored

The CLL-IPI adds weighted points for five factors in chronic lymphocytic leukemia (CLL): TP53 abnormality (4), unmutated IGHV (2), serum beta-2 microglobulin above 3.5 mg/L (2), advanced stage (1) and age over 65 (1). The 0 to 10 total falls into one of four risk groups.

Not a medical device. Not a diagnosis or dosing recommendation.

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Hematology calculators
The International CLL-IPI working group · 2016
The CLL-IPI formula
Worked examples
Frequently asked questions

What is the CLL-IPI?

The CLL-IPI is the International Prognostic Index for chronic lymphocytic leukemia. An international working group published it in Lancet Oncology in 2016, combining genetic, laboratory and clinical factors into one weighted score.

Magent's calculator adds the points for the flags and values you enter, returns the total out of 10, and returns a risk_group: low (0–1), intermediate (2–3), high (4–6) or very_high (7–10).

It is a different index from the IPI used in aggressive lymphoma, despite the shared name.

This page explains the arithmetic. It doesn't say what a score means for a particular person.

The CLL-IPI formula

TP53 abnormal (del(17p) and/or TP53 mutation)   4
IGHV unmutated                                  2
Serum beta-2 microglobulin > 3.5 mg/L           2
Advanced stage (Binet B/C or Rai I–IV)          1
Age > 65                                        1
CLL-IPI = sum · maximum 10
low 0–1 · intermediate 2–3 · high 4–6 · very_high 7–10

Exact expression the calculator uses:

CLL-IPI = tp53_abnormal 4 + ighv_unmutated 2 + beta2_microglobulin_gt_3_5 2 + advanced_stage 1 + age_gt_65 1; International CLL-IPI working group 2016; max 10; low 0-1, intermediate 2-3, high 4-6, very_high 7-10

Inputs

Input	Meaning	Accepted range
`tp53_abnormal`	del(17p) and/or TP53 mutation, as you assign it	true or false
`ighv_unmutated`	Unmutated IGHV, as you assign it	true or false
`beta2_microglobulin_mg_l`	Serum beta-2 microglobulin, mg/L	0.2 to 40
`advanced_stage`	Binet B/C or Rai I–IV (false is Binet A / Rai 0)	true or false
`age`	Age in years, a whole number	18 to 120

How the scoring works

TP53: an abnormality (deletion of 17p, a TP53 mutation, or both) scores 4.
IGHV: unmutated scores 2.
Beta-2 microglobulin: above 3.5 mg/L scores 2. Exactly 3.5 scores 0.
Stage: Binet B or C, or Rai I to IV, scores 1.
Age: over 65 scores 1. Exactly 65 scores 0.
Add the five items for a total from 0 to 10.
Group: 0–1 low, 2–3 intermediate, 4–6 high, 7–10 very_high.

TP53 carries the most weight on its own: a TP53 abnormality with nothing else already reaches the high group.

Units

Beta-2 microglobulin is in mg/L and age in whole years. The other three inputs are true or false. A missing value or a value outside its range is rejected with an error. The calculator returns the total, the maximum of 10, the risk group, the age and beta-2 microglobulin used, and the points for each factor.

Worked examples

These use Magent's own expected values for the calculator. The baseline is age 50, beta-2 microglobulin 2.0 mg/L and all three flags false, which scores 0 (low).

Example 1: no adverse factors

TP53 0 + IGHV 0 + beta-2 microglobulin 2.0 → 0 + stage 0 + age 50 → 0.
Total 0 → low.

Example 2: one factor at a time

TP53 abnormal → 4, high.
IGHV unmutated → 2, intermediate.
Beta-2 microglobulin 4.0 → 2, intermediate. At exactly 3.5 → 0, low.
Advanced stage → 1, low.
Age 66 → 1, low. Age 65 → 0, low.

Example 3: two or three factors

IGHV unmutated + advanced stage: 2 + 1 = 3 → intermediate.
TP53 abnormal + IGHV unmutated: 4 + 2 = 6 → high.
TP53 abnormal + IGHV unmutated + beta-2 microglobulin 4.0: 4 + 2 + 2 = 8 → very_high.

Example 4: all five factors

TP53 4 + IGHV 2 + beta-2 microglobulin 4.0 → 2 + advanced stage 1 + age 66 → 1.
Total 10 → very_high.

History of the CLL-IPI

The index comes from the International CLL-IPI working group, An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data, Lancet Oncology, 2016 (volume 17, issue 6, pages 779–790). The abstract describes pooling individual patient data from phase 3 trials run in France, Germany, Poland, the UK and the USA, with overall survival as the endpoint. Five independent factors emerged (TP53 status, IGHV mutational status, serum beta-2 microglobulin, clinical stage and age), and a weighted grading of them gave four risk groups. The index was then checked in two outside datasets, one from the Mayo Clinic and one from Scandinavia.

When it's used

The CLL-IPI combines results that are often gathered when CLL is first assessed: TP53 and IGHV testing, beta-2 microglobulin, Binet or Rai stage and age.

Where it's used

The inputs come from blood tests, genetic testing of the leukemia cells and clinical staging. The calculator itself needs just the five values.

Who uses it

The person using the calculator sets the TP53, IGHV and stage flags from existing results and enters beta-2 microglobulin and age. The calculator adds the points and assigns the group.

Limits of the calculation

The calculator doesn't test TP53 or IGHV, measure beta-2 microglobulin, or stage the disease. Each flag and value comes from the person entering it.
It's the 2016 CLL-IPI. It isn't the lymphoma IPI, the MIPI, or Rai or Binet stage on its own.
The risk group is a label for a range of totals. It doesn't choose a course of care.
This page doesn't say what to do with a score.

Clinical decisions belong to a qualified clinician who knows the patient.

IPI is the Shipp five-factor International Prognostic Index for aggressive non-Hodgkin lymphoma.
MIPI is the simplified Mantle Cell Lymphoma International Prognostic Index.
FLIPI is the Follicular Lymphoma International Prognostic Index.

Glossary

TP53 abnormality: deletion of 17p and/or a mutation in the TP53 gene.
IGHV: immunoglobulin heavy-chain variable region genes; scored when unmutated.
Beta-2 microglobulin: a serum protein, entered in mg/L.
Binet and Rai: two clinical staging systems for CLL. Binet A or Rai 0 is not advanced.

Common mistakes

Using the lymphoma IPI. The CLL-IPI has its own five factors.
Scoring beta-2 microglobulin at 3.5. It scores above 3.5, not at it.
Scoring age 65. Age must be over 65.
Giving every factor 1 point. TP53 is worth 4, IGHV and beta-2 microglobulin 2 each.

Source

International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779-790. DOI: 10.1016/S1470-2045(16)30029-8. PMID: 27185642

Frequently asked questions

How is the CLL-IPI calculated?

Add 4 for a TP53 abnormality, 2 for unmutated IGHV, 2 for beta-2 microglobulin above 3.5 mg/L, 1 for advanced stage and 1 for age over 65.

What are the CLL-IPI risk groups?

0–1 low, 2–3 intermediate, 4–6 high and 7–10 very high.

Is the CLL-IPI the same as the IPI for lymphoma?

No. The lymphoma IPI is a separate index with different factors.

What is the highest CLL-IPI score?

10, with all five factors present.

Does age 65 score a point?

No. Age must be over 65.