Re:starting the clock or not?

[Guest guest]

Dear Helene,

I think one should never generalise on such things, here is my personal view:

I got bad markers so treatment was inevitable even at one time I was prepare to go straight into paliative care rather than have chemo. I have been all alone on my CLL path very careful about treatment and putting quality of life first than anything else as I knew that was important to me.

It is almost 7 years since I was diagnosed, but took three years before I found all my markers to realise the type of CLL I had. In my case I think the fact that I was careful with my choice of low doses chemo that kept my quality of life well balanced.

Now that everything has failed and my consultant thinks I am a very healthy person who could cope with a transplant even at almost 64, I am heading that way with the eyes very open knowing I might not survive the year, but at least I feel something can be learn from the experience, if I survive the SCT, then CLL will be controled in a way that drugs have not been able to control, some drugs do more damage than others even they also attack the CLL, like fluradabine damage the 'T' cells, Chlorambucil is very hard on the marrow, we can help alongside by having a healthy life style.

When I was in hospital for 4 weeks during August with two infections and the reactivation of CMV I lost a lot of weight and muscle with it, well now I got a physiotherapist to teach me exercises to build up my muscles in different parts of the body so when I have the problem again (during the transplant time) I will be stronger and prepare to do the right thing avoinding some of the difficulties I had during that time.

Living every day in full takes away the worry of how long we will live and somehow in my case I stop thinking about CLL in terms of short or long life.

You said 'starting the clock or not' well when the marrow is packed with lymphocyte cells and no other cells have space to work and produce, like platelets and haemoglobin, then there is nothing you can do but start some treatment to clean up the marrow and let the cells to be produced there, if we chose no to like I was prepare to do years ago, our body can not cope and we can not survive with low platelets and haemoglobin it is as simple as that.

best regards

Chonette (UK)

Chonette dx 10-02 (aged 57)unmutated, CD38 19%, ZAP70 9%,2004 Prednisolone 8 weeks 50 mg. a day,2005 Prednisolone 8 weeks 50 mg.a day, followed bylow doses chlorambucil (2 mg.),2006 Rituximab and low doses chlorambucil (6 mg. a day 14 days on 14 daysoff) 6 rounds,2007 Low doses Rituximab,2007 Fluradabine Lite, HDMP,. Rituximab 200 mg. monthly (5 rounds)Partial Remission, multiple pea size nodes on neck,Started 16 week Campath/HDMP Protocol in June 2008, to follow SCTCMV activation plus two other infections end week 8th of Campath.Hopitalised for 4 weeks. 2 months gap to allow body to recoverDec 2008 - HDMP to reduce nodes, bone marrow clean - no more Campath neededSCT penciled for February

[Guest guest]

Helene, don't know if it will help, but my husband has a pretty aggressive disease (11q) but we have been treating it as a chronic disease since 2001. He receives Rituxan only, currently on a protocol of one infusion every 3 months. So far this has achieved great QOL and has kept the disease under control. That is our experience and may not translate to anyone else, and of course can change at any time. BethOne site keeps you connected to all your email: AOL Mail, Gmail, and Mail. Try it now.

[Guest guest]

This is a real toughy - last week was the first time I heard anyone (Dr. Keating) imply that TX at the appropriate time may not only give you a CR or PR, which we all know, but may actually increase your time.

This was the first time I heard anyone say that.

The issue of when to start was easy until now. You started not to soon, because it was assumed to make no difference to your longevity, and so you did not want to muck of your system before it was needed. Now, if we are to believe that early treatment has an impact on longevity, it's a WHOLE NEW BALLGAME.

A Good Credit Score is 700 or Above. See yours in just 2 easy steps!

[Guest guest]

Just as a discussion point, if we make treatment decisions based on

the premise of delaying it in order to delaying the start of a

survival clock, are we not assuming that timing of treatment does not

matter in the outcomes?

Generally speaking, a so-called deep (and longer lasting) CR (MRD) is

more likely to occur when the disease state is less advanced. I'm not

suggesting that this mean we should treat early, but there seems a

benefit - in the long run - from treating before the condition gets

too advanced.

This perception (all that it is) appears to be supported by the FCR

study posted ealier - outcomes by stage:

copying: ... The largest benefit for FCR was observed in Binet stage

A and B with regard to CR, ORR and PFS (A: p=0.01, B: p<0.0001). "

http://ash.confex.com/ash/2008/webprogram/Paper9237.html

Again, the above is meant for discussion purposes only ... I have no

strong view on this, nor am I qualified to have on. Also how timing

of therapy might related to management aproaches to CLL could be a

different story.

Karl

[Guest guest]

Karl,

In asking this question I in NO WAY mean to imply that we should

delay treatment when it is necessary.

What I am interested in is: once it is necessary (however we and our

doctors arrive at that determination)...then are we " on a clock " ...or

on a long-term management scheme?

The most optimal moment to begin treatment is a whole other topic,

and probably art more than science...and has many medical and

psychological components. I don't mean to open that can of worms in

this thread.

The responses to the topic so far have been interesting and

stimulating. I hope there will be more.

I will also note here to others who responded, that I also do not

mean to suggest that any individual IS the median. No individual may

be. But general population guides are all we have to go by to

figure " odds " of particular treatments working...and of long-term

survival. There is no way to know. There is only the information we

have to use as a guide. Certainly, we all look at medians in the

sense that if treatment " a " has a median PFS of 6 years and treatment

be has a median PFS of 6 months, we are more likely, other things

being equal to choose treatment " a " . Likewise, our doctors are

starting to use prognostic markers to get general ideas about

response to treatment, who should use what, etc. In addition to

clinical picture of each person, they are also reading the research

and looking at medians as well as other stats.

I hope there will be lots more takes and opinions on this - I think

all the posts have been so valuable.

Thanks, Helene

[Guest guest]

The thing to remember regarding the differences in stage is that

everyone on this trial required treatment as per current guidelines.

This does not address the question regarding treating early versus

not.

The current cooperative group trial will address this, randomizing

unmutated CLL patients to immediate versus deferred therapy using FR

in both arms. My guess, as suggested by Karl, is that earlier

treatment will allow reduction of the tumor burden before the second

hits and changes are likely to occur that will make the CLL cells

resistant to treatment. But only time will tell.

Rick Furman, MD

>

> Just as a discussion point, if we make treatment decisions based on

> the premise of delaying it in order to delaying the start of a

> survival clock, are we not assuming that timing of treatment does

not

> matter in the outcomes?

>

> Generally speaking, a so-called deep (and longer lasting) CR (MRD)

is

> more likely to occur when the disease state is less advanced. I'm

not

> suggesting that this mean we should treat early, but there seems a

> benefit - in the long run - from treating before the condition gets

> too advanced.

>

> This perception (all that it is) appears to be supported by the FCR

> study posted ealier - outcomes by stage:

>

> copying: ... The largest benefit for FCR was observed in Binet

stage

> A and B with regard to CR, ORR and PFS (A: p=0.01, B: p<0.0001). "

>

> http://ash.confex.com/ash/2008/webprogram/Paper9237.html

>

> Again, the above is meant for discussion purposes only ... I have

no

> strong view on this, nor am I qualified to have on. Also how

timing

> of therapy might related to management aproaches to CLL could be a

> different story.

>

> Karl

>

[Guest guest]

Hi Helene, I didn't take your comments to be promotional. : )

Regarding the mean as a reference point, it should be noted that

online persons tend to be younger than the general population with

NHL, and presumably CLL. And overall survival is calculated based on

death from any cause, which skews the mean downward for the general

CLL/NHL population. (What would be the mean survial for anyone at

age 65? Ten years?)

-- Recently, Stanford reported a mean survival for follicular NHL to

be ~17 years, much better than the often cited 8 or 10 yrs. But the

mean age treated at that center was also much younger ... I think it

was 49, versus 65 years.

Coming back to the survival clock: Perhaps you agree that " When

treatment is necessary " is in the eye of the beholder. Interesting,

to me anyway, that some investigators have used this measure as a

study endpoint to compare outcomes across studies. I'm aware that

FDA doesn't like this endpoint because When to Treat is not well

defined, hard to measure objectively.

All the best,

Karl

> In asking this question I in NO WAY mean to imply that we should

> delay treatment when it is necessary.

>

>

[Guest guest]

Karl,

You make a very good point about measuring survival over long periods

in a population that starts old middle-aged to old. I always wonder

when they report median survival, e.g. for Stage 0 of 10 or 12

years...if the median age at diagnosis is 70, then the median

survival wouldn't be that much better for someone without CLL. So,

how much does age factor into the survival figures?

And your other point is correct to - the start and endpoints in CLL

studies are moving targets. Everything starts with " from diagnosis " ,

but many CLLers could have just as easily been diagnosed a year or

two sooner, or later, just depending on when they happened to get a

blood test and a doctor who noticed.

My husband, for example, had a blood test for surgery in 3/07 that

had elevated lymphs and WBC. No one said anything. But if they had,

then his date of diagnosis would be year earlier.

Thanks for those points.

Helene

[Guest guest]

Helene, Thanks.

For follicular lymphoma (an indolent lymphoma) the FLIPI is used to

estimate risk / prognosis ... but I think mainly for comparisons of

outcomes across different studies, not to predict risk for individual

patients.

Anyhow, age is one of the factors in this prognostic index. See

http://www.lymphomation.org/prognosis.htm#FLIPI

All the best.

Karl