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Disappointing results

The results from my latest bone marrow test were disappointing in that the proportion of ph+ cells went up from 27% to 44% (in 3 months), having fallen from 94% in the previous 3 months. My consultant was concerned that this might mean Dasatinib won't be an effective treatment for me, particularly as I'm only on 20mg and usually only manage 5 - 6 weeks on treatment before having to come off for 3 - 4 weeks due to low platelets and neutrophils. We're due to discuss my options further, possibly including stem cell transplant, at my next appointment in a fortnight.

Has anybody else had similar experiences in terms of interrupted treatment and/or erratic results from bone marrow tests? - are there any examples of a good response being achieved again after a disappointing one?

Thanks for any helpful advice / comments.

Alyson

Hello Alyson

Sorry to hear you have had disappointing results. I don't know much about eratic results early on in treatment, but I would urge you to get a second opinion from one of the specialist CML centres about the options available to you, especially if transplant may be on the agenda. Your consultant will be able to refer you to another centre, and an appointment should be reasonably quick.

You don't say where you are treated, and you may already be in a large centre such as Hammersmith [Prof Apperley], Newcastle [Dr O'Brien] or Glasgow [Professor Holyoake], but if not - get there quickly! Most haematologists only see a few patients with CML, and if you look as if you are responding in any way bar completely straightforwardly, then I think a CML specialist's opinion is vital.

Best of luck - let us know how it all goes, and I hope someone can give you more information about erratic early results soon.

Janet

Dear Alyson,

I am sorry to hear this. Given your results are from a bmb (bone marrow biobsy) I would not say that it is likely to be wrong or as in the case of peripheral blood pcr's- sometime erratic. The biopsy is subjected to 'cytogenetics' testing and is therefore very reliable.

I would say though that given you cannot tolerate more than 20mgs of dasatinib -the standard dose is 100mg per day- then it is perhaps not surprising that you are showing a sub-optimal response. For any drug to work in the way it should you have to metabolise it at or near to the optimal dose. Of course there are individual responses to dose to consider but 20 mg and then a 5-6 weeks without any therapy is not the best way to see an optimal response...or maintain a response.
I am surprised that you have not been given the option of maintaining your neutrophils with GCSF - or maybe you have? I know many patients are able to support their white cells whilst on TKI therapy by injecting GCSF. You do not say how low your platelets drop but most of us can tolerate quite low levels.
this sort of supportive therapy would allow you to maintain consistency of your dose of dasatinib instead of having to interrupt therapy all the time. This is not a strategy that is recommended. Before considering transplant I would assume your doctor would try to find out if you would respond to nilotinib a little better?
Have you had a mutations test done?

I agree with Janet that you should talk to your consultant about a second opinion. I am not sure where you are treated but if not at one of the major CML centres then I suggest you ask for a referral asap. It might well be that you do need to think about transplant... and you really do want to be at a centre that performs a lot of these should you go down that route... I would have no hesitation in recommending Hammersmith Hospital which is where I had my 'mini' transplant in 2003.

Please consider all options before this though... you need to understand:
1. why you are not able to tolerate more than 20 mgs.... and/or try supportive therapy (GCSF) to help you stay on 20mgs without breaks and....
2. rule out or identify any mutations- a fairly simple test.
3. get a referral to a major cml centre if you are not at one already
4. try nilotinib

Good luck and please keep us updated,

Sandy

Hi Alyson

I'm sporry to hear you are having problems with low counts. I had exactly the same problem and like Sandy said G-CSF would have been an option if it were only the white counts and neuts. Like you however I also had a problem with platelets, they averaged between 10 and 20. Low doses of the drugs and lots of drug holidays meant that my bcr/abl just kept rising.

I would love to be able to say they found a drug option that worked but that was not the case and I had a transplant 10 months ago. I am doing very well and although transplant should only be considered when all other options have been tried don't be frightened of it.

Good luck

Helen

Thank you all for the helpful information.
I have been treated at Chesterfield Royal Hospital since being diagnosed at the end of January 2009. I have also been referred to the Hallamshire in Sheffield and seen Dr. Snowden in respect of the possibility of a mini-transplant (my brother is fortunately a full match).
My neutrophils have been as low as 0.5 and platelets as low as 29, although last week they were 1.1 and 70, so hopefully I might manage a bit longer on the medication this time.
I've not had a mutations test, but would this still be relevant as I had achieved a MCR (from 94% to 27%) after the first 3 months on Dasatinib (which had included a couple of breaks totalling 4 weeks)?

Alyson

Hi Alyson,
I am glad to hear you have a good sibling match. My younger brother was a good match for me and my transplant went well. Please read my diary for details of the non-myeloblative sct (so called 'mini' transplant- several centres in the UK are now part of this study which is led by Hammersmith and Queen Elizabeth's in Birmingham). You could ask if Dr. Snowden at Sheffield offers this much safer and increasingly successful form of sct. Enough of transplant!

I do hope your latest blood cell result means that you are showing signs that you can tolerate dasatinib for longer... the major goal is to keep the plasma levels of the active drug constant over time.
The fact that you achieved a major response within the first 3 months is a good sign, but that fact alone would not rule out a mutation. So I would say that a test would be a good idea in order to clear the picture and rule out a mutation. The fact that you have heamatological intolerance to the drug and your neutrophils and platelets are both affected is a complication that needs careful management.
Has your doctor suggested you should be looking at trying nilotinib should these problems continue?

The good news is that your neutrophils are over 1, and a platelet count of 70 is pretty good as these things go... so as you say you might be seeing signs of overcoming Haematological intolerance. It also might mean that the drug is very good at dealing with PH+ cells and over time you will have normal cells -not affected by the drug- which will grow in number and allow you to keep taking the drug.
I hope you a not too worried by all this.. although of course you must be.... but if you understand your own particular responses and have all the information possible you will be able to make a more informed choice should you need to change therapy.

Sandy