The 100k myth - Where did the "Treat CLL when the Absolute Lymphocyte Count (ALC) gets above 100(thousand)" myth come from?

The 100k myth - Where did the "Treat CLL when the Absolute Lymphocyte Count (ALC) gets above 100(thousand)" myth come from?

A few days ago, Len Keck posted the extract from the International Standard Criteria for Diagnosis & Treatment of CLL, published by the International Working Group on CLL (iWCLL) and last updated in 2008 on the criteria for starting treatment:

ncbi.nlm.nih.gov/pubmed/182...

Len pointed out that this document, prepared and reviewed by the best international experts on CLL, states at the end of the section on when to start treatment: "Patients with CLL may present with a markedly elevated leukocyte count; however, the symptoms associated with leukocyte aggregates that develop in patients with acute leukemia rarely occur in patients with CLL. Therefore, the absolute lymphocyte count should not be used as the sole indicator for treatment."

Section 4.2, Second-line treatment decisions commences: "In general, second-line treatment decisions follow the same indications as those used for initiation of first-line treatment."

So what are the indications for treatment the first or second (and subsequent) times around? Here they are in full!

"4. Indications for treatment

4.1. Primary treatment decisions

Criteria for initiating treatment may vary depending on whether or not the patient is treated in a clinical trial (Table 2). In general practice, newly diagnosed patients with asymptomatic early-stage disease (Rai 0, Binet A) should be monitored without therapy

unless they have evidence of disease progression.

Active disease should be clearly documented for protocol therapy. At least one of the following criteria should be met:

1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

2. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly

3. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy

4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of less than 30*109/L (30 000/L), LDT should not be used as a single parameter to define a treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.

5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (see section 10.2).

6. Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:

a. Unintentional weight loss of 10% or more within the previous 6 months;

b. significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual activities);

c. fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection; or

d. night sweats for more than 1 month without evidence of infection.

Hypogammaglobulinemia or monoclonal or oligoclonal paraproteinemia does not by itself constitute a basis for initiating therapy. However, it is recommended to assess the change of these protein abnormalities if patients are treated.

Patients with CLL may present with a markedly elevated leukocyte count; however, the symptoms associated with leukocyte aggregates that develop in patients with acute leukemia rarely occur in patients with CLL. Therefore, the absolute lymphocyte count should not be used as the sole indicator for treatment."

Notice what's absent? Yes, there's absolutely no mention of starting treatment when the lymphocyte count climbs over 100(thousand). If you search through the entire document, the only references you'll find to counts of 100 are haemoglobin (under 100) and platelets (under 100(thousand)) as these are important indicators.

More pinned posts on this subject:

Why we need to track the absolute lymphocyte count (ALC) not white blood cell count (WBC)

healthunlocked.com/cllsuppo...

When to Treat

healthunlocked.com/cllsuppo...

When do white count numbers trigger treatment?

healthunlocked.com/cllsuppo...

How high can you go? (And what does it matter?

healthunlocked.com/cllsuppo...

So can anyone tell me where this myth came from?

Neil

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5 Replies

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  • Good post Neil and clearly whilst there's no compelling clinical evidence to suggest the 100,000 lymphocyte level should be a sole indicator for treatment, I confess it's the number that would make me nervous. Like a special birthday I didn't want.

    I think it's the tumour lysis syndrome that worries me. The concern that my renal plumbing couldn't handle the mass flush exodus! Of course every case is different and co-morbidities must play a part (though I'm not sure they're given enough signifance but maybe I missed that).

    I'm just hoping I make it to a 100 but not in lymphocyte numbers!

    Regards,

    Newdawn

  • Hi Neil,

    The short answer is ignorance. A corollary to ignorance is fear, on the part of both patient and oncologist. Ignorance and fear work hand in hand to create a false need to treat for the CLL inexperienced oncologist and the psychological pressure on the patient to "do something". It runs against most empirical treatment outcomes for the vast majority of cancers to simply wait and watch. It also took awhile to get enough data to suggest that early treatment did not equate to better outcome. The tipping point of using 100k WBC or ALC was probably arbitrary and reflected a false emphasis on cancer activity in the peripheral blood and the perception for what those cells were doing to patient health.

    The question of when to most effectively treat CLL is once again becoming a relevant, if not timely question, given advances in new therapies and a better understanding for CLL biology.

    WWW

  • Neil

    Great post and the short answer is I have no idea! But it might be from way back

    I could not get the Blood Journal link at top of this post to work (says page not found)....but if this article is from 2008....what have the Working Group been doing since?! Or have they dis-banded?

    Do new drugs require the group to re-think?

    Andy

  • Hi Andy,

    There are a number of versions of the document. I've changed the link to the PubMed article, which was correct as of 15th Dec 2008. (There were a couple of minor corrections to the document through 2008).

    iWCLL meet annually and last met early this month in Sydney, Australia. Brian Koffman ( CLLSociety.org ) gave a presentation to the expert doctors from a patient's perspective and has covered the meeting. Patient Power have also provided some coverage.

    There are sure to be updates to the document as more experience with the newer drugs is gained, but for now, this is the latest version that I know of.

    Neil

  • Neil

    Thanks - link worked!

    Andy

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