Calc Function

    • Calcs that help predict probability of a diseaseDiagnosis
    • Subcategory of 'Diagnosis' designed to be very sensitiveRule Out
    • Disease is diagnosed: prognosticate to guide treatmentPrognosis
    • Numerical inputs and outputsFormula
    • Med treatment and moreTreatment
    • Suggested protocolsAlgorithm

    Disease

    Select...

    Specialty

    Select...

    Chief Complaint

    Select...

    Organ System

    Select...

    Patent Pending

    International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI)

    Stratifies patients with chronic lymphocytic leukemia into four risk categories.
    Favorite
    When to Use
    Pearls/Pitfalls
    Why Use

    Patients with new diagnosis of chronic lymphocytic leukemia (CLL), to estimate prognosis and time to first treatment.

    • Developed using patient data from before use of targeted agents such as ibrutinib and venetoclax, which are known to have greater efficacy in patients with TP53 alterations.
    • While treatment type was not an independent factor in the CLL-IPI, TP53 status was, and thus the use of novel agents may have an effect not currently measured in the CLL-IPI.

    Many patients with CLL will have an indolent course and not require treatment for many years, while others will have a shorter time to first treatment. The CLL-IPI combines clinical, laboratory and genetic risk factors into a single score that can be used to help estimate time to first treatment as well as overall survival.

    ≤65 years
    0
    >65 years
    +1
    Binet A or Rai 0
    0
    Binet B-C or Rai I-IV
    +1
    ≤3.5
    0
    >3.5
    +2
    Mutated
    0
    Unmutated
    +2
    No abnormalities
    0
    Deletion 17p (FISH) and/or TP53 mutation (sequencing)
    +4

    Result:

    Please fill out required fields.

    Next Steps
    Evidence
    Creator Insights

    Advice

    • The CLL-IPI categorizes patients into four risk groups from low risk to very high risk. The decision to treat should not be based on the risk score, since it has not been evaluated for that purpose.
    • Indications for treatment remain the same, but higher risk patients may warrant closer initial monitoring.

    Management

    • Guidelines have not yet incorporated the CLL-IPI scoring system into management algorithms.
    • Risk categories should be used to inform prognosis, and closer monitoring for higher risk patients should be considered.
    • Notably, survival estimates were based on assessments from before the era of targeted therapies for CLL, and this should be taken into consideration when counseling patients.

    Formula

    Addition of the selected criteria:

    Criteria

    Selection

    Points

    Age

    ≤65 years

    0

    >65 years

    1

    Clinical stage

    Binet A or Rai 0

    0

    Binet B-C or Rai I-IV

    1

    Serum β2 microglobulin, mg/L (or µg/mL)

    ≤3.5

    0

    >3.5

    2

    IGHV mutational status

    Mutated

    0

    Unmutated

    2

    TP53 status

    No abnormalities

    0

    Deletion 17p (FISH) and/or TP53 mutation (sequencing)

    4

    Facts & Figures

    Interpretation:

    CLL-IPI Score

    Risk

    5-year survival

    0-1

    Low risk

    93.2%

    2-3

    Intermediate risk

    79.3%

    4-6

    High risk

    63.3%

    7-10

    Very high risk

    23.3%

     

    Evidence Appraisal

    The CLL-IPI was described in 2016 using data on 3,472 patients from 8 clinical trials ranging from 1997-2007. The patients were randomly divided with 2/3 (2,308) in the training set and 1/3 (1,164) in the validation set. The main endpoint for statistical analysis was overall survival as calculated by the Kaplan-Meier method.

    After deriving a weighted score based on multivariate Cox regression they calculated a discriminatory statistic c=0.72 (where 1.0 is full discrimination) and the different subgroups' survivals were statistically different from one another. The internal validation confirmed these results.

    The CLL-IPI was independently validated in two follow-up studies in 2016 (Gentile and Da Cunha-Bang). In the first follow-up study, 858 patients from Italy who were not part of clinical trials were used to validate the CLL-IPI and confirmed the previous results; however, most of the patients were not evaluable due to missing data. In the second study, 1,514 patients from a Danish CLL registry were evaluated and confirmed the prognostic value of the CLL-IPI.

    Dr. Michael Hallek

    From the Creator

    Why did you develop the CLL-IPI? Was there a particular clinical experience or patient encounter that inspired you to create this tool for clinicians?

    We developed the CLL-IPI because we realized that the clinical staging systems did not separate high risk patients well enough in the era of new therapies (chemoimmunotherapies) (Pflug et al, Blood 2014).

    What pearls, pitfalls and/or tips do you have for users of the CLL-IPI? Do you know of cases when it has been applied, interpreted, or used inappropriately?

    The score should be applied for prognostication but not for determining treatment indication. As of today, indication for treatment is determined by symptoms of disease (and sometimes clinical staging).

    What recommendations do you have for doctors once they have applied the CLL-IPI? Are there any adjustments or updates you would make to the score based on new data or practice changes?

    The CLL-IPI will be evaluated in the era of novel targeted agents to see whether it applies for patients treated with agents such as ibrutinib, idelalisib, or venetoclax.

    How do you use the CLL-IPI in your own clinical practice? Can you give an example of a scenario in which you use it?

    I use it for all CLL patients.

    Any other research in the pipeline that you’re particularly excited about?

    I am excited about the potent therapeutic efficacy of novel agents in CLL, and by studies of clonal evolution of CLL under targeted therapies, as well as strategies to prevent it.

    About the Creator

    Michael Hallek, MD, is an internist specializing in hematology and oncology in Cologne, Germany. He also serves as chair of the internal medicine department at the University of Cologne and director of the Center for Integrated Oncology. Dr. Hallek's primary research interests include the development of specific molecular therapies for leukemia.

    To view Dr. Michael Hallek's publications, visit PubMed

    Content Contributors
    About the Creator
    Dr. Michael Hallek
    Content Contributors