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Talk of a BMT

Hello All

Today i have been to Hammersmith hospital for my 6 weekly visit,i have been told that my July PCR test result is at 2.4% which is about normal for me give or take +/- .2-3% it has been around this level for 2.5 years.

I started on Imatinib 400mg June 2006 then went on to Dasatinib 100mg for a year and now back on Imatinib 600mg for the last 4-5 months.

I have been told i should now be thinking about having a transplant as my Leaukemia levels won't come down and at the age of 39 it's better to do it sooner than later.

Having now read up about it i must say it sounds quite frightening, and at this moment in time feel i don't want to except that it may come to this.

Quite happy and thankful to stay at a stubborn 2-3% thanks.

Has your consultant talked to you about trying any of the other available drugs before going the BMT route? It sounds like dasatinib did not work for you, but there are other drug options.

I can totally understand your trepidation about having a transplant. My husband's consultant has been talking about BMT on and off for the last few months, which I don't mind admitting has freaked me out a bit. But alongside that, we've also been told that if his PCR doesn't drop enough, it's very likely they'll be able to try all the other drugs first.

IF you do need to go the transplant route there are lots of friendly people on this site who have had a transplant and come out the other side who can tell you more about it.

All the best

On Dasatinib my PCR levels didn't increase just stayed the same but as i was in a clinical trial they deemed me to have a sub-optimal response,having been on the said drug for a year.

So back on Imatinib but at a increased dose now (600mg) and still no decrease but blood counts are stable and no mutation, the consultant said she didn't think increasing to 800mg a day or 'nilotinib' would help?

There was no mention of availability of other drugs.

Must say having been told yesterday that the company i work for has gone into administration and then at hospital saying i should now be looking at having a BMT i feel quite low.

Is it possible to 'plateau' as it seems i have but remain stable or is it probable that i will lose response to the drug.

The consultants know best but i'm not sure that a BMT is the answer just yet.

Thanks.

I understand why you are so reluctant to go for a BMT ... if the sort being offered is the traditional 'full monty'!
I am surprised your consultant has not offered
a. 800mg imatinib
or
b. nilotinib

before you consider transplant options. Maybe this is a cost issue? as nilotinib (and dasatinib) are not through NICE appraisal yet and therefore NHS Trusts and PCT's etc. are not yet 'obliged' to pay.

However, you may want to push the argument and ask for:

a. plasma level testing (see the EUTOS programme link onright
column above Newswire) if this has not already been done.
If your plasma levels are found to be sub-optimal then
there would be a case for an increase in dose.

b. nilotinib. This drug has been shown to be more effective
for some individuals. So it might be worthwhile to try
given you have not been given a reason for your pcr's
sticking at 2% or so... unless your plasma levels are
sub-optimal?

c. ask about the possibility of you enrolling in the RIC-sct +
imatinib + DLI study. I had this form of transplant at HH
in 2003 after I lost my response to imatinib. (read my
diary on home page. As far as I am aware, HH are still
recruiting patients for this study but they tend to offer
it to 'older' patients rather than those under 45/50 as
It does take longer to reach a 'cure' that the trad. sct
but......... the risk of transplant related mortality is
much less.

But first ask if they have tested plasma levels. The optimal level is at or above 1000 ng per ml. This is a simple test to perform.... see link to EUTOS (European Treatment Outcome Study)

I am sorry to hear you also have worries about work etc. this is obviously not good news and can only add to the pressure you feel.

Try to get to the bottom of the reason for your sub-optimal response and ask for more information from your consultant. They do probably 'know best' but then if I had not done my own research when I was first diagnosed in December '98, I would not have been able to access imatinib in '99 and would have followed my consultants very strong advice to have a full BMT! If I had blindly followed that advice I am not sure what would have happened in my case.

Sandy

Sandy

Thank you Sandy for taking the time to give me such well-explained advice.

I shall now look into plasma levels and the other excellent advice you have given me and start to ask the relevent questions now that i'm well-informed.

The consultant said the reason not trying 'Nilotinib' is because of my age, being slightly younger than the average CML patient and also it works in more or less the same way as one of the 2 drugs i've tried so probably wouldn't see a benefit?

I'd imagine half the battle is knowing what to ask and what to push for... seems like the financial cost paints the real picture as per usual.

Lots of reading up for me.

Thanks for all advice given.

I am surprised your consultant has told you that both dasatinib and nilotinib work in the same way. It is true that they are both Tyrosine Kinase Inhibitors and as such target protein (Tyrosine Kinase) signaling within the Ph+ cell.

All TKI's work by blocking the signal (or switch off the signal) which causes the PH+ cell to proliferate.

However, dasatinib targets more signalling pathways (both ABL and SRC) than nilotinib (ABL and KIT- same as imatinib) but nilotinib targets and blocks the cell signal in a more efficient way than imatinib.

So... briefly, nilotinib is a similar drug to imatinib but its chemical structure has been 'tweeked'- so it is able to 'fit' more effectively (tightly) into the binding pocket of the Ph+ cell and so is more effective at blocking the protein signal ........... in other words it is better at turning off the switch and so the abnormal PH+ cell dies.

Try wikipedia for explanations of cell signaling and how TKI's like imatinib/dasatinib/nilotinib block those signals.

Yes... a lot of reading/research for you, but the more you know the better you can make a truly informed decision (along side your doctor) about the best therapy possible for you.

Sandy ;o)

Nilotnib was discounted for me because I am Diabetic,without a full history its hard to decide treatment options,but dont let it put you off asking why your options are limited.
Mike

Hi,

I am puzzled at your doctor's comment that you should start thinking about a transplant.

He is the doctor and he should be looking at all the alternatives for you. What about the many drugs that are not yet approved. Does he have access to all the clinical trials that you might join.

By the way, did he tell you about the mortality statistics of BMTs? How about this sobering one ... 50% of BMT patients are dead within 5 years.

As long as you can maintain your current level of response (I really don't know what 2.4% means) but if it means that you are in CCR and can maintain this level over time, you will do as well as those of us who are at a 3 log reduction or PCRU.

Zavie

Zavie Miller (age 71)
Ottawa, Canada
dxd AUG/99
Gleevec since MAR/27/01 (400 mg)
CCR SEP/01. #102 in Zero Club
3.6 log reduction Sep/08
3.8 log reduction May/09

Thanks for all the information.

yes i am in CCR and my PCR's for the last couple of years are always around 2%.

I shall go back to hospital in 5 weeks armed with this new info and advice and see what response i get,hopefully something more positive than the last visit.

Thanks again.

If it is any help trying to get your consultant to try the plasma level testing then the following may help.
I was diagnosed Spring 07 with CML and on 400mgs Imatinib from april '07. By 6 months I had reached 0.139% PCR but then over next 6 months the PCr readings started creeping up. My consultant wasn't aware of the plasma level testing offered from Bordeaux and I showed him the literature that had been posted by Sandy on this site. He agreed to test which revealed low trough plasma level of Imatinib of only 511 nano grams per ml, only about half of the minumum recommended level. Following return of results he agreed to upping my dose to 600mgs of Imatininb per day and generally since then I've been on a succession of falling PCR readings. Plasma level on retest was much nearer 1000 nano grams per ml. Fortunately I've been very lucky with side effects even on higher dose. There seem to be all sorts of factors at work in where plasma level ends up so even if you are on higher imatinib dose now it is still worth getting test done. I know test is now available from UK centres as well as Bordeaux. Regards
Andy