Ask an expert about chronic myeloid leukaemia (CML) 

We marked Blood Cancer Awareness Month (September) with a webchat on chronic myeloid leukaemia (CML). This is quite a rare type of cancer, with 750 new cases diagnosed in the UK each year.

Our expert was consultant haematologist Dr Andres Virchis. He is the clinical lead for CML at UCLH and runs a weekly clinic for patients with CML at University College Hospital Macmillan Cancer Centre. He manages patients in a variety of clinical situations and treats patients using all tyrosine kinase inhibitors (TKI) – the type of drugs that are typically used as anticancer drugs. UCLH is specialist centre for the treatment of blood cancers across north and east London and west Essex. We are also building a new facility which will make UCLH the largest specialist treatment centre for blood diseases in Europe.

The conversation focussed on living with CML and managing the condition from diagnosis to treatment.

Below is a transcript of the web chat.

1:09 UCLH: 
Good afternoon and welcome to our web chat. We will begin at 15:00 (3pm), but you can submit your questions now in preparation for the chat. Please note: your questions will not appear in the main chat window until after 15:00 (3pm)

Dr Andres Virchis will be joining us to take your questions on chronic myeloid leukaemia (CML) and will try to answer as many questions as possible within the hour long web chat.
3:01 Dr Andres Virchis: 
Good afternoon, I'm Dr Virchis and am ready to take any of your questions. This is a new one on me and looking forward to it!
3:01 [Comment From Susan: ] 
I have had CML for over 10 years and had a stem cell transplant 8 years ago. My donor was my sister. I want to know if having a sibling’s cells makes the patient become more like their donor - both in looks and mannerisms. I have definitely become more like my sister (or has she become more like me) as we both get older. Is it just family history or is it the stem cells at work? I am not 100% donor cells though and have low level residual disease. On a side note - I am a UCLH patient, but we’ve never met as I was seen at the RFH until recently. Prof. Stephen Mackinnon is my doctor.
3:01 Dr Andres Virchis: 
Dear Susan, a really interesting question. I suspect you have become more like your sister due to as you say family history. The fact that she was found to be a match and subsequently your donor has probably brought you closer together. The stem cells only impact on you blood cells and immune system, which is now identical to your sister. If your donor had been a brother or a male then of course a bit of you would always be a ‘man’ so to speak, which some of my female patients in the past have found to be an interesting concept?
3:07 [Comment From Marianne: ] 
I have read about Prof. Holyoake's team in Glasgow who have been working for many years on finding ways to target the leukaemic stem cells (LSCs) that seem to escape the effects of TKIs - at least in the vast majority of CML patients. What do you think about this research? Are they getting closer to finding a way of targeting these cells?
3:07 Dr Andres Virchis: 
Dear Marianne, this research is not only very interesting but I think will ultimately result in a significant development in the treatment of CML. Although the TKIs are largely extremely useful in depleting and supressing the CML to very low levels, often borderline detectable even with sensitive PCR, they are only effective on dividing cells. As such the CML stem cell is relatively resistant and this is why TKI treatment is not ‘curative’. If we are able to target the stem cell in addition to TKI therapy then we may have the ability to cure CML medically, something that in the past was only achievable with stem cell transplants.
3:14 [Comment From Trevor: ] 
What is the best treatment for CML – tablet medication or stem cell transplant? Or both?
3:14 Dr Andres Virchis: 
Dear Trevor. I would say TKI treatment overall. Although a stem cell transplant is still the only potential treatment that can be curative it has very significant side effects, both short term and potentially long term, and a not insignificant mortality risk. As such TKIs, which are generally highly effective and well tolerated, offer for the majority, a better longer term outcome. However that is not to say there is no longer a role for stem cell transplants, for example in the rare instance of highly resistant CML or where none of the treatments are tolerable; or in the rare circumstance s of transformation to blast crisis.
3:30 [Comment From Faye: ] 
I have some questions about managing CML. Having listened online to the conference from Manchester on Saturday, much of the focus was on treatment of CML & possibly stopping treatment. I feel there was a lack of dealing with side effects. What I did note, was that sideeffects may increase in intensity, on stopping TKI treatment, for up to 6 months after discontinuation.
3:30 [Comment From Faye: ] 
1)Why does there seem to be a lack of treating these sideeffects...both during TKI treatment and on discontinuation? Having sideeffects seriously reduces the quality of life for many and may lead changing a TKI which is working, but intolerable. From my own perspective, I stopped Imatinib mid 2008 (after 3 years treatment) because of sideeffects and relapsed within 18 months. During that time I still had bone and joint pain. I was never offered an alternative TKI on stopping Imatinib. I later found out that other TKIs had been available.
3:30 [Comment From Faye: ] 
Also I was curious, 2) When secondary TKIs came about, they were said to be 300 times stronger than Imatinib, the standard dose of which is 400mg, yet for eg. Dasatinib std dose is 100mg. Would the equivalent not be about 4mg? Is dasatinib being over prescribed?
3:30 Dr Andres Virchis: 
Dear Faye, I will take your points, all very good, and try to answer them as best I can. I personally try and focus a lot on potential side effects and I think this is extremely important. As in most patients we are talking about a likely long treatment we have to make sure that as well as concentrating on the efficacy, that is controlling the CML, their treatment is tolerable.
Given the number of TKI available (actually four at the moment) I try and ensure that I find the right one for each of my patients. Also I frequently use dose reductions to manage side effects as CML lends itself very well to this. What I mean by this is as the end result is achieving a very low BCR-ABL level the dose to achieve this is less important as long as it’s ‘doing the job’. Therefore reducing doses can help with side effects without affecting response. An alternative is of course to also change the TKI to find as I’ve said the right one for the patient.
The issue of side effects increasing after discontinuation mainly relates to stopping and staying off imatinib, which in some can cause muscle and joint pains.
Finally regarding dosing the number of milligrams is related only to the specific drug and is not transferrable to others. You are right about the 2nd generation TKIs, such as dasatinib, being more potent but that is from a molecular stand point in the test tube. The number of milligrams is simply the weight of that specific drug formulation, so doesn’t relate to the strength of that drug.
3:32 [Comment From Lihua: ] 
Which is the best treatment for CML? My consultant has given me TKI medication which has normalised my blood count. I’d like a cure though ideally as I do not want to have to take medication all of my life. Is this possible?
3:32 Dr Andres Virchis: 
Dear Lihua, I hope I have covered you questions with my answers to soem of the previous questions.
3:37 [Comment From Gordon: ] 
Good afternoon Dr Virchis. I was excited to read that NICE have now recommended bosutinib for routine treatment in the NHS. Is this drug now the best available therapy? Is it available as a treatment at UCLH?
3:38 Dr Andres Virchis: 
Dear Gordon, I was very excited too. I wouldn’t say it is the best available therapy but by now having access to 4 very effective TKIs I will be able to ensure that not only will my patients have an effective treatment but if there are side effects I have a lot of options. Alternatively if my patient has other medical complaints I can make sure I hopefully choose a treatment most suited to them. And yes bosutinib is available at UCLH.
3:44 [Comment From Emma: ] 
I should be most grateful if Dr Virchis could kindly give indicate whether there are any particular suggestive symptoms to look out for, and any screening methods such as blood tests, for this condition - in an elderly patient.
3:44 Dr Andres Virchis: 
Dear Emma, frequently CML is diagnosed as an incidental finding. As it’s more common in older people they are more likely to have blood tests for other things, for example a recent patient of mine was diagnosed after routine blood tests before a hip operation. However symptoms to look out for are, in no particular order: looking pale from anaemia, abdominal bloating from an enlarged spleen (can also cause reduced appetite and feeling full as the stomach can be ‘squashed’ by the large spleen), sweats/night sweats, fatigue, unexplained weight loss.
3:45 [Comment From Jack: ] 
Hi my question has not appeared re generic imatinib
3:46 Dr Andres Virchis: 
Dear Jack, I've been inundated with questions, including many on generic imatinib, and will get to this shortly so please hold tight.
3:46 [Comment From Alison: ] 
My mother, who we lost ten years ago, had CML. I do not have CML, but how likely is it that my daughter will develop it?
3:48 Dr Andres Virchis: 
Dear Alison, there is absolutely no indication of CML being inherited in any way or even being familial so to speak. So everybody's risk is essentially the same as everybody else's.
3:58 [Comment From David: ] 
Some patients I've spoken to who take branded imatinib are worried about moving to a generic. Can you advise what questions they should be asking their doctor and should they ask for more frequent pcr tests for first few months?
3:58 [Comment From Jack: ] 
How safe will generic imatinib be, im currently doing very well on imatinib but have read patients in canada lost response when switched to generic form
3:58 [Comment FromAnonymous: ] 
How safe is generic imatinib actually going to be? Im doing very well on glivec and have read from canada that patients did lose response when switching to generic.
3:59 Dr Andres Virchis: 
There have been a lot of questions about generic imatinib. Generic drugs in general are exactly the same drug but manufactured by other companies other than the initial developer. Sometimes the formulation might be different, that is what makes up the medicine, but not the drug itself; for example it may be as a capsule of a tablet. Any generic imatinib that comes to market will need to be licenced by the EMA (European Medicines Agency) and to achieve this they have to show that they are effective. I personally at the moment have no concerns; however in time if I had a patient who was concerned I would certainly offer them more frequent PCR monitoring, in the initial period, as a reassurance.
4:06 [Comment From David: ] 
With generic imatinib soon to be with us, is there value in targeting CML with more potent too drugs, and then migrating them to generic imatinib for maintenance. Could this approach help to achieve better cost benefits ?
4:06 Dr Andres Virchis: 
Dear David, this is a very interesting question. There has been a lot of debate about using 2nd generation TKIs, such as nilotinib, as first line treatment instead of imatinib. Certainly they are more effective in the short term at achieving deeper and faster reductions overall in the CML clone. The controversy is still around whether this results in longer term benefit. With the cost saving with generic imatinib an option might be as you say choosing an appropriate 2nd generation TKI (nilotinib, dasatinib or bosutinib) for a patient and then when a deep molecular response is achieved switch to generic imatinib to ‘maintain’. There may be trials in the future to explore this.
4:11 [Comment From Brenda: ] 
My CML is well into the chronic phase and is generally quite well controlled although I get very tired now and then. Is it likely to get worse as I get older or will it stay the same now?
4:14 Dr Andres Virchis: 
Dear Brenda. If you have achieved a good response to your treatment, I presume you are on a TKI such as imatinib, then the evidence so far from the early trials of imatinib back in the late 90s / early 2000s is that the majority of patients (>80%) remain well and stable at 10 years of follow up. Our hope is that for many this will continue to be the case for their lifetime.
4:14 [Comment From Jack: ] 
Should we have not had trials here 1st for generic imatinib to check as effective?
4:14 Dr Andres Virchis: 
Dear Jack, in order for the generic manufacturers to get a licence they do need to submit data from studies to the EMA showing that their product is effective without any unexpected side effects.
I think your question was the last so I would like to thank everybody for their contributions. Best wishes to you all.
4:23 [Comment From Faye: ] 
Thanks for your answers

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