When people talk about "more aggressive" CLL, what do they mean?

Is it to do with time to treatment or resistance to treatment?

[AussieNeil Administrator]

More aggressive usually means a shorter time to treatment, but CLL is always full of surprises.

If a treatment no longer works effectively, then that person's CLL is said to be refractory to that treatment.

Neil

[Hidden in reply to AussieNeil]

Hi, Would it be fair to say that there was a correlation between the time to treatment and hving bad prognostic markers?

[Cllcanada Top Poster CURE Hero in reply to Hidden]

We are talking groups here... not individuals... this is important to understand.

Time to Treatment (TTT) factors include, age, gender, Rai stage at diagnosis, IGHV gene stereotype, mutation, TP53, ATM, 17p and 11q deletions, high Zap70 and or high CD38 percents.

Further, bone marrow involvement and immunoglobulin levels, short telomere length... and a host of new genetic damage/mutation.

CLLtopics has a good article... most data still applies, although the risk buckets have blurred, due to the findings and importance of subclones...

clltopics.org/PI/Type.htm

One maker, 17p delete or TP 53 gene mutated or nonfunctional ...indicates that the patient will respond poorly to standard chemo immunotherapy regimes...

so these patients are often treated with alternate therapies and depending on age, recommended for a clinical trial or perhaps a stem cell transplant.

However, for 11q, data from the German CLL8 trial indicated these patients do well on FCR therapy, which appears to move them from higher risk group to a lower risk group, since they respond well to this combo.

You can learn more about complexity of this and the new role of sub clones from this paper...

nature.com/leu/journal/v28/...

[Hidden]

Thanks very much for the links. Would you say someone with 17p deletion would go straight to treatment at diagnosis or is impossible to say?

[Cllcanada Top Poster CURE Hero]

Very individualistic, some 17p patients perhaps go into treat in a year or 18 months from diagnosis, but then again, how advanced was their CLL at diagnosis??

I know some 17p- that haven't been treated in 3 years and a couple more haven't been treated in over 5 years... New treatments are very effective for 17p patients and there are many more in the pipeline...

For each of the old FISH makers in all groups there is both good and bad. 13q is considered a good marker, but if the genetic damage is large and the RB1 gene is removed then that 13q is more aggressive.

We can't change our genetics or our age, but we can improve our overall health, getting fit and enjoying life... the healthier you are when treatment rolls around, the easier it will be generally...

Comorbidities play a large role in CLL, something that is often overlooked by the patient...

medscape.com/viewarticle/73...

[Cllcanada Top Poster CURE Hero]

Informative video from Andrew and Patient Power

patientpower.info/video/the...

[UKfulloflife]

Don't know if this is any help.... I was diagnosed in June 2012 and on a fairly casual W&W. By July 2013 was in pretty urgent need of treatment. My CLL specialist was at pains to ensure that I understood that this did NOT mean that my CLL was 'more aggressive' than anyone elses, or that I would require further treatment any sooner than anyone else. Afraid I don't know (and at the moment don't want to know!) anything about deletions, mutations or whatever, so can't comment on the relationship to these. I had 4 cycles of treatment on a trial and am now in full clinical remission, with a prognosis of 3 - 4 years before the necessity for further treatment.

[zentangle]

Thanks for your answer fulloflife,

Would you mind me asking what "pretty urgent need of treatment" looked like?

Regards,

zentangle

[lankisterguy Volunteer]

Hi zentangle,

Here are the IWCLL 2008 guidelines for treatment, these are often used for qualifying to start treatment in clinical trials, and are somewhat dense for casual reading, but if you can wade through the medical jargon, it defines need to treat.

bloodjournal.org/content/bl...

Here is the pertinent text:

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. Studies from the French Cooperative Group on CLL,46 the Cancer and Leukemia

Group B,47 the Spanish Group PETHEMA,48 and the Medical Research Council 48 in the United Kingdom in patients with early-stage disease confirm that the use of alkylating agents in patients with early-stage disease does not prolong survival.

This result was confirmed by a meta-analysis.49 In one study, treated patients with early-stage disease had an increased frequency of fatal epithelial cancers compared with untreated patients.

46 Therefore, the potential benefit, if any, of an early intervention therapy with antileukemia drugs, alone or in combination with monoclonal antibodies, requires further study.

Whereas patients at intermediate (stages I and II) and high risk (stages III and IV) according to the modified Rai classification or at Binet stage B or C usually benefit from the initiation of treatment, some of these patients (in particular Rai intermediate risk or Binet stage B) can be monitored without therapy until they have evidence for progressive or symptomatic disease. 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.

4.2. Second-line treatment decisions

In general, second-line treatment decisions follow the same

indications as those used for initiation of first-line treatment.

Patients who have resistant disease, a short time to progression

after the first treatment, and/or leukemia cells with del(17p) often

do not respond to standard chemotherapy and have a relatively

short survival. Therefore, such patients should be offered investigative

clinical protocols, including allogeneic hematopoietic stem

cell transplantation.50-54

[zentangle]

Thanks for this. It seems a long time since I originally posted.

Regards

zentangle