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PCR at Hammersmith following allo BMT

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Hi Everyone,

my wife is approaching 11 years post BMT and all is generally going well. We've just received her 6 monthly PCR result from Hammersmith which is 0.003 % (0.001% International Scale). I was a little surprised as previous results (e.g. April) showed 0.001% (0% International Scale). The consultant was great and explained that there is no clinical significance of this change and that at such low levels it's very common to see such minor fluctuations- he wasn't worried at all, and will test as normal again in 6 months.

Nonetheless, I still can't help feeling disappointed and worrying that this represents a rising PCR (despite still being MR5), and can't seem to stop worrying/thinking! I kinda wish the test could be taken again so that I see 0%!

I'm really just seeking some reassurance.

Have others who have undergone a BMT experience such PCR fluctuations so long after their BMT?

Thanks

Ol

Hi Ollie,

I know a rise is always worrying - and in your mind you may be thinking "it's tripled!" but you must remember that 0.001% means 1 in one hundred thousand. 0.003% is three in one hundred thousand. Minuscule amounts.

It's really a statistical anomaly. If you ran the same PCR test again, immediately after the first one was done, you may have found a 0.000%, a 0.005% etc. etc. The differences really are tiny at that level of exceptionally deep response.

If I were you I would actually be more comfortable with a 0.003% result than a 0.000% ... it shows that the test is working, and that there's not something funny going on. I once got a 0.000% result and frankly didn't believe it and put it down to some sort of clerical error, and I was pretty much right as the next result went back to my usual range.

David.

Dear David,

 

thanks very much for your reply, and advice- it was very reassuring.You're quite right, that I should view the 0.003 (0.001%IS) as a limitation of the test rather than anything more clinically meaningful; Its just that nagging thought that 'a relapse has to start somewhere'...but this is my irrational/emotional side kicking in- silly. Two years after my wife's BMT she had a rising PCR and experienced a molecular relapse; 4 escalating doses of DLI worked a treat (with no GvHD either), and I guess I'm still haunted/paranoid by that relatively early set back.

Best wishes

 

Ollie

Hi Ollie,

I also had an SCT at HH in 2003 and eventually went on to have 4 DLI's at around 14months post SCT.  I had a reduced intensity SCT so it was expected that I would see rising Bcr-Abl levels at some point. The 4th DLI did the trick and knocked out the remaining residual disease.... that was in 2006. All my following PCR results remained negative until HH upgraded their PCR methodology which meant that they could dig deeper into the molecular world and low and behold their new 'machine' found I still had low levels of Bcr-Abl. Suddenly my results were 0.001% and I was pretty worried. However, that level has remained stable for the last 2 or 3 years so I have accepted that I although I am not 'cured' in the normal sense of the word, but rather my disease is very adequately controlled by my new (donor) immune system so I no longer worry at all. 

I understand your anxieties though - my partner and our daughter are mostly 'on alert' for any signs that I may 'relapse'. It is natural when you have experienced watching helplessly as someone you love undergoes an SCT. Fortunately, even if ,at some point in the future, I experience a molecular relapse, I know that I can either have another DLI of donor lymphocytes (HH still have enough for one more) or I can access one of the TKIs again.

I hope my experience (I am consistently stable at 0.001%) will help put your fears into perspective,

Sandy

Hi Sandy,

thnaks for sharing your experience, it's very reassuring to hear. My wife had a BMT is Sweden (where's she's from), and had all of her follow up over there until the last 2 years where HH have taken over. The swedes reported he PCR as negative but HH report as 0.001; so I figure that the difference is down to the enhanced sensitivity of HH. I read an interesting paper on PCR testing of long term allo BMT CML patients; some of these patients got down to MR7! But as David and our consultant said, as you get down to such low level the lability of the test is less and less. I wonder what digital PCR using DNA will show... : /

Incidentally, we've just been referred to the late effects clinic run by Dr Salooja at HH, I think they start seeing patients post-10 years BMT. Have you had experience there? I was really impressed- Dr Salooja is hypervigilant (like me!) about any sign/symptom and has a great understanding of all late effects and how to manage post BMT patients; we've had a range of tests (pulmonary, gynae, bloods etc) all of which have been fine. Very reassuring to know there's a dedicated team to support us in the future.

Thanks again,

Ollie

Hi Ollie

 

I'd just like to add that next week marks 9 years since my allo SCT for CML. Initially I was negative for about 3/4 years although I was not 100% donor cells. 

I had DLI as I wasn't 100 % donor cells straight away. The DLI was 7 months post transplant. However almost immediately I developed horrendous arthritis which persists even now. As I had so much treatment for the joint pain the DLI was never going to work.

I think I went from a negative PCR to low positive after about 4 years and it's remained low and fairly steady since then. It has fluctuated by about a log. My last count in June had gone up a log but they still didn't want to do anything. I am back on steroids for the joints so they wouldn't do anything anyway. I'm due another test in December.

Most of the people who had a transplant around the same time have low level residual disease. I do think that the more detailed testing is finding those elusive cells.

I'm interested to know what other complications people can experience so far out from the transplant.

Best wishes to you and your wife.

 

Susan

Hi Susan,

thanks for your message. It does seem that PCR can bounce along the bottom at low levels.

in regards to late effects of BMT, there are potentially quite a few which we were told about- and any organ/system can be effected. I think cardiovascular disease, endocrine & pulmonary dysfunction and second malignancies are the most frequent. It's worth bearing in mind that while the relative risk for second cancers is high (i.e. Risk compared to the general population) the total absolute risk is low. My understanding is that it largely depends on a range of factors such as conditioning regime (e.g. TBI, bulsulphan, cyclophosphamide etc), presence of cGVHD, age at transplant also any medical conditions prior to BMT, and of course baseline genetic risk factors. It's worth talking to your consultant about your individual risk so that these risks can be monitored and managed.

Ollie 

Hi David, Sandy and Susan

 

I remember from watching the video by Prof. Apperley and Letisia at the 2015 CML patients day that if one receives a 'dodgy' PCR result (Prof Apperley's term!) then the test should be repeated to explore a possible trend upwards. My wife's next PCR is due as normal in 6 months; but I wondered if given there's been an increase from 0.001% (0%IS) in April to 0.003 (0.001% IS) in October that a test sooner would be more appropriate?

The Dr at HH that I contacted about result didn't seem to think a repeat PCR test was necessary sooner (I didn't ask them directly), but I just want to know what their reasons were, given that whilst 0.001 to 0.003 is a minor increase, its still an increase. The Drs at HH have been great and I am quite an annoying partner that asks lots of questions during appointments, and don't want to annoy the wonderful Drs at HH or suggest that I'm questioning their professional judgement- but I just feel that some explanation would be helpful to understand. I'd appreciate any thoughts others might have, and advice on how to approach this topic with the Dr.

Do you think our increase in PCR is just too minor to worry about at all, and so a repeat PCR sooner just isn't clinically necessary?

 

Thanks again,

 

Ollie

Hi Ollie,

At the levels you're talking about, you start to push the limits of what the available technology can do. Had the blood been taken from your wife's other arm, you may have got a slightly different result. Given we are talking about 2 extra positive cells in one hundred thousand (0.001 to 0.003) I really think that you have to look at this as an acceptable margin of error. The tests, while very advanced, are not perfect.

Let me give you an example of a 'dodgy' result from my own results.

  • May 2015: 0.018%
  • August 2015: undetectable (0%)
  • November 2015: 0.021%

That 'undetectable' was, in my opinion, nonsense and I returned to a more realistic range a the next test and my downwards trend stays nice and stable besides one anomaly. Actually, 3 months after the November one I went up a bit more, than at the following one down a fair bit.

I really don't think you need to worry. Your wife has got an extremely low PCR result and the difference between 0.001% and 0.003% should be viewed in your head as an extra two cells in one hundred thousand ... and absolute not as a tripling of a previous result. The numbers just don't make sense when looked at like that.

So whilst it's great that you are worrying about this (patients or carers who don't worry can neglect things they should look after!), I think the proportionate response is to view this as a minuscule increase at what are already levels which test the capabilities of the testing technology. If you get another increase next time, then it would be a good time to talk to your doctor. 3 significant rises in a row would be a cause for a bit of concern but you are miles away from that point now.

 

David.

Thanks David,

 That's a very helpful way of looking at it, and thanks for your example. I think as we have been through one molecular relapse in 2008, any minor increase in BCR-ABL, even minor fluctuations, causes us some anxiety.  Wishing you a great weekend, Ollie 

I had  MUD BMT and then 5 years after had a rising PCR.  In my case rapidly rising. I went on imatanib and had rapid success. I'm now 26 months in on the DESTINY trial and have had 14 months drug free and undetectable.

Hi Darley

Not wanting to deviate too far off topic here, but how are you feeling having been off TKI's for so long?

Are you feeling slightly/much different from being on Imatinib? If so, in what areas, joints, fatigue etc?

Look forward to hearing back.

John

Hi John

How are you doing now? Really hope the side effects have abated,

best

Chrissie