Confusion about time for treatment

[Guest guest]

What determines need for treatment? Rising WBC and ALC-

doubling in less than 6 months - or how a patient feels,

examination and absence of physical symptoms upon

examination?

My WBC has gone from 21000 to 41000 in four months and my

ALC has doubled in the same time period. Yet I have no

symptoms other than chronic sinus infection, that has

improved considerably. Should I be worried?

Thanks.

Q

[Guest guest]

I am wondering the same thing. My WBC doubled in the last 5

months and my hematologist said I would probably need

treatment in 6-12 months. Then I went for a second opinion

with a CLL specialist at Fox Chase and he said he would not

treat me until I was symptomatic. Does it just depend on

the doctor? And what does he mean by symptomatic? I got

the impression it meant when the symptoms were so bad I

could not bear it.

Thanks, Bonnie

Q wrote:

/message/16100

[Guest guest]

My local ONC told me over 6 months ago that I would need

treatment in 6 months and then Dr. Byrd told me 3 months ago

that I was doing fine so no reason to even come back and see

him for 6 months. I am not sure how I interpret all of that

but I am feeling fine even though I do have somewhat

enlarged lymph glands in the neck but not as large as they

were 3 or 4 months ago. Trust your instincts and your CLL

specialist if you have one. Good luck!

Ron

Dx May 2010

Unmutated CD38 positive

[Guest guest]

Your counts are still on the low side and counts can vary up

and down on their own. What you and your doctor probably

want to do is schedule another blood test sooner rather than

later and see if this is a trend, in which case you would

likely have a faster-moving CLL. After hearing the pros

and cons, you may decide you want to proceed to treatment.

Dr. Furman talks about the doctor's " art " of deciding when

to treat, which I think refers to the fact that even when

objective criteria like doubling time or high white counts

exist (i.e. " disease load " or aggressiveness) they should be

tempered by the patient's described quality of life and what

he or she wants to do.

There's an art to our (patient) side also. We go through

our processes and adjustments with this disease, we read,

think, maybe cry or rage or shake, and we make the final

decision—which might of course include asking the doctor to

make it for us!

I wanted treatment when my swollen lymphatic nodes hampered

my breathing. I might have waited longer but I chose not

to. I was just too uncomfortable and .. scared -- and the

doctor agreed with me.

There are other considerations like the still-unanswered

questions about whether earlier intervention may improve

chances with some patients for longer and better remissions

but so far that's not been shown to be true.

Best,

Frances Friedman

[Guest guest]

HI ,

I also had no symptoms, not even a chronic infection, but I

had to seek treatment because of steeply rising counts.

However, it's not just ALC doubling in less than six months.

My counts had already climbed much higher than yours (well

over 100,000) when my ALC doubling time started dropping.

Just wait and watch for continued steep increasing. You

might want to request more frequent testing, too, but keep

in mind that your results will vary some anyway, so it's the

consistently steeply rising counts that will tell you

whether you need to start giving serious thought to

treatment.

What does your onc say?

Karni

[Guest guest]

,

I received Rituximab treatment when my WBC was at 20K (went

to 4K after the first or second treatment); however, the

fatigue was extreme, had a bout with shingles and lymph

nodes here and there were growing and causing pain (prior to

treatment). Since I feel normal I won't get treatment again

(hopefully) until the fatigue or other symptoms return--even

if my WBC rises way above what it was.

Chris

[Guest guest]

Karni, My onc says I should have less frequent blood counts-

no more than every three or four months apart. No treatment

without at least B symptoms - extreme fatigue and/or night

sweats. Also I have a lot of nodes in stomach, hip, back,

under arm, etc but they are very tiny and only show up on

the Cat scan. My liver and spleen are not involved. The onc

also said not to pay a lot of attention to the prognosticators-

11q deletion, Pos Zap, unmutated but neg CD38. But I find it

difficult not to after all the reading I have done.

[Guest guest]

Appreciate your comments, Frances.

My gut tells me that earlier intervention could improve the

outcomes for some patients (perhaps younger pts) with CLL

given FCR therapy - that this is an important clinical

question to test.

I was told that a proposal to test this hypothesis was not

received well by investigators. (But this is merely

ancedotal - a remark from a CLL advocate in a cooperative

group)

A report on the importance of age in treatment decisions:

http://www.nccn.org/about/news/ebulletin/2011-09-19/cll_therapy.asp

Karl

> There are other considerations like the still-unanswered

> questions about whether earlier intervention may improve

> chances with some patients for longer and better remissions

> but so far that's not been shown to be true.

>

> Best,

> Frances Friedman

[Guest guest]

The recent Mayo study comparing CLL Experts may shed some

light on this.

The study found that the Time To First Treatment (TTFT) was

longer in the case of CLL 'expert' hematologists rather than

non-expert doctors.

The study basically states-

among early-stage patients (Rai 0-I), median TTFT for CLL

expert doctors was 9.2 vs 6.1 years for the non-expert and

overall survival (OS) was 10.5 years vs 8.8 years.

So, from this study it looks like the experts doctors treat

later by nearly 3 years.

But, while the overall survival (OS) in the 'expert' treated

doctors is longer by nearly two years it would be wrong to

assume that the later treatment was a contributing factor.

It may have an effect, it may not have an effect.

http://onlinelibrary.wiley.com/doi/10.1002/cncr.26474/full

HTH

~chris

[Guest guest]

There IS some evidence that there may be benefit from

'early' treatment in medium to high risk CLL patients....

the OTHER Mayo study,/s that might shed some light on this

topic,,,,that in some cases, possibly even nearly half, or

at least the medium to more aggressive types, that are

showing benefit of early treatment. Overall survival is

what we'd like to see, and that with no treatment, however,

as we learn more about CLL, I doubt many patients would opt

for that study if it meant holding back on a possible even

slightly helpful treatment that would not land them in worse

shape, just to see how long they might last without ever

needing treatment.

afterall, rapid progression is possible, and happens with

CLL and then choices are limited, treatment longer and

harsher, and end results less satisfying.... where's the

benefit there?

A lot has been said, repeated and drummed into us that 'we

don't want to treat too early'... that there is no proof

that treating 'early' will help. these studies seem to be

showing that in certain groups of patients its looking like

it may be of value while not necessarily having the once

dreaded consequences of further clonal evolution, or

lessening future therapy choices.

the studies below investigates such things as disease

progression and times of remission with certain treatments

in each risk group. and it would seem without some of the

dreaded consequences once thought to result from 'early

treatment' may not necessarily be what we had thought.

http://www.mayoclinic.org/news2008-rst/5067.html

this study while small, shows that early intervention in

HIGHER RISK patients has benefit in disease course and

appears not to be as great a hazard as we may think...

depending on many factors, which should be included in any

evaluation, this group used alemtuzemab and rituxan.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849723/

http://jco.ascopubs.org/content/24/28/4634.full

While most studies and trials do not deal with this issue,

it's one we would do well to heed... CLONAL EVOLUTION from

time of diagnosis, based on various abnormalities.....This

article reports a retrospective investigation of patients

whose blood was and is stored at Mayo, and the ongoing

rates of survival, ttft as well as the RATE OF CLONAL

EVOLUTION. they state that adjusting formulae have been

used to ameliorate the relatively small (100-150) number of

patients....... Since most studies deal only with the

abnormality known at the time of trial initiation, and some

don't categorize survival, etc based on these same factors,

we are left to wonder.

we know that CLL is a heterogeneous disease, and not even

all patients who own a particular clonal evolution will

behave in exactly the same way, but these studies, I believe

have at least shown that in SOME CLL patients earlier,

perhaps a little less aggressive, intervention may indeed

have benefit. Avoiding further clonal evolution would be

one benefit, lengthening the time to harsher treatment might

be another, or even time in a good remission, without

progression? overall survival, I doubt anyone wants to

hang around and see how that would pan out, at least not if

they KNEW that ahead of time.

be well, beth fillman

[Guest guest]

All chemo does some harm. According to everything I've read

so far, there is absolutely no definitive evidence that

early intervention improves anyone's chances of surviving

longer, which is why most hem./oncologists will not treat

early. The doctors recommending early intervention for CLL

are mostly non-specialists and there has been some evidence

that patients in the same Rai stages treated with early

interventions did not survive as long as those who deferred

treatment, which would make perfect sense since one way CLL

may evolve is by undergoing molecular changes as a result of

chemo that cause surviving cells to be more resistant. As

for intervening earlier with patients with poor prognostics,

I came across this on a CIG website: " But remember that even

when comparing the survival curves for a bad prognostic

marker versus a good one, the curves always overlap and

physicians do not know where an individual will be on the

curve. "

[Guest guest]

This post highlights a very important feature to avoid of

phase II trials. In the cited trial, they took patients

with high risk features and gave them a brief course

alemtuzumab and rituximab. They then stated that these

patients were able to go a longer to until they needed

treatment than a group of similar patients.

The thing to point out, is that these patients already did

receive treatment. They are no longer untreated. So this

study really just shows that rituximab and alemtuzumab are

tolerable and generate high response rates.

Even if you allowed comparison between two phase II studies,

this study might show that patients who get treated when

they do not need treatment can go longer until they receive

their next treatment compared to what would have been their

first treatment. For all we know, the cells that relapse

will be resistant and not responsive. (I do doubt this

though).

Please be careful when looking at phase II studies. We

still do not have any data regarding early versus delayed

intervention in modern times. There is one European study

that is on-going, but it may not have generalizable

applicability due to several issues with their choice of

prognostic markers.

Rick Furman, MD

Beth Fillman wrote:

/message/16123

[Guest guest]

I completely disagree with your conclusions based on the

results of this study. If you look at the data, 12 months

after therapy none of the measured markers, such as T-clls

and NK cells, had returned to normal. In addition, there

were increases in FISH abnormalities after treatment, such

as the dreaded 17p.

Although the study concludes that further research is

needed, the authors are certainly not stating that overall

survival or morbidity will be reduced through this method of

early treatment. They see the research as " promising. " Maybe

so, maybe not.

Personally, I can't imagine why they would use alemtuzumab,

knowing how devastating this drug is for T-cells.

Ron

Beth Fillman wrote:

/message/16123

[Guest guest]

Does this also apply if FISH shows you have " dreaded " 17P

deletion? And what success if any can occur with treatment

with the 17P deletion? I go to see Dr Link at Iowa

City for a second opinion and frankly my mental condition is

not good with this deletion plus 13. My WBC has almost

tripled from 35000 to 89000 late June to last week. Other

blood work is OK and I feel OK. I'm wondering if treatment

will do any good or not?

Rick Furman, MD, wrote:

/message/16130

[Guest guest]

,

I, too, had no B symptoms, but, like I said, my counts were

much higher than yours and were very erratic. Weekly or bi-

weekly CBCs were showing extremely steep ups and downs with

the trend clearly upward. If those points on my ALC

doubling time chart had been further apart in time, I

wouldn't have felt treatment was called for just yet. I

remember reading that ALC doubling time is significant only

when counts get a lot higher than yours, so that might be

why your onc doesn't seem overly concerned right now. But

maybe he'd be open to the idea of having monthly ones for a

couple of months just for now - you could tell him it would

ease your mind a lot, and then you'd feel much more

comfortable about having tests only quarterly or so. Perhaps

that would work for you.

Best,

Karni

[Guest guest]

This study of 930 patients at MDACC was just published

today, Oct 3rd, 2011

" Multivariable Model for Time to First Treatment in

Patients With Chronic Lymphocytic Leukemia "

It states:

" The following were independently associated with shorter

time to first treatment:

three involved lymph node sites, increased size of cervical

lymph nodes, presence of 17p deletion or 11q deletion by

FISH, increased serum lactate dehydrogenase, and unmutated

IGHV mutation status. "

Source Abstract JCO: http://tinyurl.com/5roenzo

~chris

[Guest guest]

As of now, this pertains to all CLL patients. I do wonder

if high risk patients might benefit from early treatment,

but this is only theory until it is proven. Since treatment

has its downsides, it is important to determine the best

approach through clinical trials.

Rick Furman, MD

Chapman wrote:

/message/16135

[Guest guest]

Please define " high risk. " Do you mean as per

prognosticators, genetic pre-disposition,

blood test values, etc. "

Thanks in advance.

Q

Rick Furman, MD, wrote:

> As of now, this pertains to all CLL patients. I do wonder

> if high risk patients might benefit from early treatment,

> but this is only theory until it is proven. Since treatment

> has its downsides, it is important to determine the best

> approach through clinical trials.

[Guest guest]

High risk means " high risk of progression " when it is used.

This would typically mean unmutated IgVH, zap-70 positive,

del 11q or del 17p. Individual studies will choose

different definitions.

Rick Furman, MD

Q wrote:

> Please define " high risk. " Do you mean as per

> prognosticators, genetic pre-disposition,

> blood test values, etc. "

[Guest guest]

I would be considered high risk since I have 11q, unmutated

with positive Zap-70 and age 67. However since I am only

Stage 1 perhaps that is why I am in Watch & Wait. For high

risk patients are their trials starting at Stage 1? Still

very confused.

Q

Rick Furman, MD, wrote:

> High risk means " high risk of progression " when it is used.

> This would typically mean unmutated IgVH, zap-70 positive,

> del 11q or del 17p. Individual studies will choose

> different definitions.

[Guest guest]

Q,

Do not underestimate the " High Risk " factor of " progression

rate " . Rick Furman states: " High risk means " high risk of

progression " when it is used. " High risk of progression is

not always determined by prognostic indicators such as FISH,

IgVH mutation status, CD-38% or ZAP-70. The actual

observance of how your CLL behaves over time will be the

most accurate real time measure of the threat your CLL is to

your health and need for therapy intervention.

One value of the prognosticators can be in developing a

treatment strategy that gives you an edge for best outcome.

Using myself as an example, I was led to believe I may never

need treatment due to all favorable prognosticators. My CLL

did not read the scrip and I progressed rapidly needing TX

in two and a half years. Where I believe the favorable

prognosticators (13q del., CD38 neg., IgVH 6% mutated) were

valuable to me was in the wider range of therapy choices

EXPECTED to give me a good response. Even though my limited

use of Fludara and Rituxan did their best to kill me, the

response in reducing my overall tumor burden was excellent.

I am in touch with some members with 11q del and one with

17p del., unmutated IgVH markers that are progressing slower

by years than my progression. If and when their progression

rates take off they will most likely need to be facing a

narrower set of therapy options and a diminished expectation

of response depending on factors involving not only drugs of

choice but relevant co-morbidities, vulnerability to

infection and age.

The bottom line is with the smart money betting on a better

outcome through W & W, risk factors or no. That does not mean

slacking off on strategizing for when W & W ends particularly

in the emerging age of less toxic options through Clinical

Trials.

Hope this helps,

WWW

[Guest guest]

Just to add to my confusion I asked for all blood tests from

2010 (I was diagnosed June 2011) and it looks like the WBC,

Lymphocytes, etc. were already showing signs of CLL back in

Mar. 2010. Should this be a factor or concern? My WBC went

from 15.6 to 41 in 18 months. My ALC went from 8 to 31.3 in

the same time period.

Q

Wayne Wells wrote:

/message/16148

[Guest guest]

You would be high-risk based upon the features of your

cells, but since you are only Rai Stage I, there would be no

indication for treatment. This is why I always try to

emphasize the importance of clinical disease progression and

not prognostic markers.

Rick Furman, MD

Q wrote:

> I would be considered high risk since I have 11q, unmutated

> with positive Zap-70 and age 67. However since I am only

> Stage 1 perhaps that is why I am in Watch & Wait. For high

> risk patients are their trials starting at Stage 1? Still

> very confused.

>

> Rick Furman, MD, wrote:

> > High risk means " high risk of progression " when it is used.

> > This would typically mean unmutated IgVH, zap-70 positive,

> > del 11q or del 17p. Individual studies will choose

> > different definitions.

[Guest guest]

so, high-risk does not mean treatment is needed but there is

a higher than normal incidence of needing treatment sooner

than low risk patients?

My question is this: When do you throw all the high risk

features out of the equation? Tom is multi-treated with all

high risk features including using the V3.21 gene for his

unmutated status. He is one year into the PCI trial and it

seems to be holding his CLL in a stable position. When he

had to go off trial for a fever, his lymph glands ballooned

back up within 2 days. Back on trial and they melted away

again. The WBC and #lymphs mimic his glands. Even though

he is high risk and in treatment, do these newer inhibitors

change the rules? Can he hold a remission status as long as

he is on PCI? And, if so, then is this similar to a cure or

long term remission?

Thanks to everyone for any input,

Lou

Rick Furman, MD wrote:

/message/16152

[Guest guest]

Ultimately, the answer is it is too early to tell. We do

know that CAL-101 and PCI-32765 work independently of the

prognostic markers. The duration and sustainability of the

responses is unknown.

Rick Furman, MD

Lou wrote:

/message/16157