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Is a sudden transformation from MR4 to blast crisis possible?

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Hi everyone

I've unfortunately had a setback in my CML treatment and was hoping that someone on the forum could give me advice, please.

Last month (30 June) my latest BCR-Abl test was 0.003% and MR4.5.  I've been in MMR since January 2018.

Yesterday, a complete blood count showed that I have pancytopenia:

Red Blood Cells 2.37

Haemoglobin 8.8

White Blood Cells 3.18

Platelets 98

The doctor called me in and said that this was very serious - I've never had any low blood counts before - and immediately booked me in for a bone marrow biopsy.  She also said that I must prepare for some difficult months ahead.  I have no idea why my counts are so low, but it completely freaked me out this morning when I saw my admission sheet - she had written "CML transformation" as my diagnosis, which makes me think that she believes that the disease has progressed.  I find it so hard to believe that one can go from MR4.5 to blast crisis in less than a month!

A search revealed that blast crisis often presents with pancytopenia.  This is counter-intuitive to me because I thought blast crisis would show up as a high WBC, not a low one.  The doctor also prescribed me anti-depressants and organised a session with the psychologist as she said I'll need them for the road ahead... when I spoke to the psychologist today and said that I didn't think it possible for such a quick progression in disease, he answered "Well, cancer does that.  That's how it operates."  

If anyone has any experience with this, or just some advice or kind words, I'd be so grateful.  I get the results on 8 August so it's one very long wait... and it's devastating to me that I may not have beaten CML after all.

Thank you and kind regards

Martin

Oh, Martin!  Just saw this.  All I can send you is the kind words part; I'm hoping that Trey will weigh in on substance.  (And David and Theresa.)  I am sure I am speaking for many, many others who have read your words today and are actively pulling for your well-being.  While you wait this unconscionably long time for bone marrow answers, avail yourself of the psychologist's help in dealing with the uncertainty.  I doubt very much you would get this level of interim emotional management in the US!  I dunno about the antidepressants, tho.  But, hey, short of just being sedated completely until August 8th, maybe try 'em.  Many, many times I have felt the jig was up, in some medical downturn, only to find out at the end that things aren't as bad as I feared.  My therapist once said, "Most times, things turn out all right."  At the time, many words came to mind: jejune, anodyne, cliche, trite, moron.  But, I actually found I was clinging to that, and it helped.  I also came up with one of my own (after watching too many nature shows):  "Sometimes, the wildebeest gets away."  Laastly, my best friend once, after listening to my tearful tirade over some ghastly surgery, said, "But, Kath, it's DOABLE."  Hope something here helps even a little.  Keep us posted!

I don't have any advice on this,but sending positive vibes your way.As my father who is a doc will say,let the report come then only you will know the full picture.

Martin is one of my closest friends - we met virtually on here several years ago when CML once ruled my world (no more) and we have remained very close since opening up about our diagnosis of CML and our personal lives. He’s been nothing but a shoulder and a support to me for several years - and I attribute my strength now largely to him. If anyone has any advice on this please do chime in as this is a real time of need for him...

My two cents for all of us, this stage of Martins CML affects us all and how we view our “remission”. “All is ok you're MMR and in remission you don’t have a mutation don't worry your tablets are working, take your pill this will never be a problem for you” is what we are sold/I have been sold. And referencing Martins comment from his therapist "Well, cancer does that.  That's how it operates."... well not CML for all we have been told...

I am not saying this is CML related or even Blast related. I am failing to belive that it is. How can it be that he’s been MMR for 4-5 years and MMR 4 and below for 3 of them. 1 month ago all counts are in range and then all counts are so low that it requires a transfusion and a 2nd bone marrow biopsy. How is that remotely possible in CML? I would have thought blasts in the blood would be the 1st tell, bleeding, bruising and most definitely not feeling right. Why are they monitoring BCR in the blood if BCR doesnt always correlate to Accel/Blast phase. As far as I know my great friend here has none of that. Can this really be CML? I am failing to believe it is - or is it something else unrelated possibly going on? We really need that CML support here right now. I know a lot of this is guess work but there are a lot of veterans on here that may be able to shed some light or share a similar experience. Could TKI suddenly cause blood count crashing - I am sure I have read on here that has happened but can that happen so late and in MMR +6 years. 

Hopefully this comment bumps this post at the very least as it needs some desperate support.

Alex

https://ashpublications.org/ashclinicalnews/news/3133/How-to-treat-an-ol...

Was googling and found this,seems similar to your situation

Any recent medication that may cause more TKI concentration?

Martin, I have no advice to offer, just want to say when I put myself in your place, I so feel your anxiety and stress, and so wish the result of the bone marrow biopsy will reveal nothing untoward is taking place.

I must be honest with you, the psychologist's  reply "Well, cancer does that. That's how it operates".....actually rubs me totally the wrong way. That is NOT what we want to hear when we are bewildered and afraid and don't know what the hell is going on.

12 days till August 8th....and I am sure every single one here is rooting for you to receive the result that your heart is yearning for. My very best wishes to you dear Martin.

pigeon

 

 

 

 

Hi Martin I am fairly new to the world of CML so can’t really comment much.  I pray for you for a positive outcome. Mina. 

Martin,

It's unlikely you went from MR4 to blast crisis. Blast crisis presents with very high count of blast cells (>20% of cells). You don't list your blast cell percentage. What you describe seems more like myelodysplastic syndrome (causes myelosuppression) or multiple myeloma which can occur in CML patients even in remission. It is usually associated with mutations in normal hematopoietic blood cells such as trisomy 8 or monosomy 7. Your doctor will specifically be looking for these kinds of mutations from the biopsy. It's possible the drug you are taking for CML is causing the myelosuppression (which happened to me) and stopping therapy for a while may lead to blood count rebound. Without additional data, however, it's hard to know. I do not suspect you have high blast cells. Verify to be sure.

Stay vigilant, read up on multiple myeloma and myedysplastic syndrome for background along with the article posted in this thread by An.

 I often see people referring to their blast cell count in posts in this forum; it is obviously important, but I never see any reference to it in my quarterly blood tests.

I have no idea what my blast cell count is. I have been  MR5/undetected for a while now, but don't remember ever seeing a result for blast cells in my blood test report. Should I ask for it to be tested nxt time, or is it a stupid question....sorry, I obviously have limited knowledge.

I am being treated at the Hammersmith in London, maybe someone who is being treated there can enlighten me? Thank you.

pigeon

 

They don't report,because you don't have blasts,otherwise it will be in the manual differential.

Hi Kat

Thank you so much for your kind words and for your encouragement.  I haven't made use of the antidepressants as I want to be on as little medication as possible, but I have been talking to the psychologist and finding that useful.  Short of waiting for the report, I guess there's nothing more I can do!

Thank you also for those quotes (I especially liked the wildebeest one because it is one of our South African animals!)... and as you say, often some good comes out of the medical downturns.

I really appreciate your reply!  I'll let you know what happens on 8 August.

Martin

Hi Alex

Thanks so much for your public words of encouragement and for your friendship over the years.  You have helped me so much through leukaemia and this is why this group is so important - I met a great friend I would never have had otherwise!

I agree wholeheartedly with what you say about MMR.  It makes very little sense that there can be such a jump from one month ago when it was almost undetectable.  I'm holding faith that it is TKI related as you've said - I found a few scholarly articles that pointed to people developing anaemia and even bone marrow aplasia late into treatment on imatinib.  My adverse effects on dasatinib started only after 2.5 years, so I am holding onto the hope that something similar has happened after 3 years on imatinib.

Thank you so much again Alex - will keep you posted!

Hi An 

Thanks so much for your wisdom... you're quite right that I can only wait for the report and try not to get too hyped up about what could possibly have gone wrong.  I'm also grateful for the article you sent as it shows that weird things can happen with CML, even late into therapy.

I haven't started any new drugs, but I also have a condition known as haemochromatosis that requires me to have blood drawn on a regular basis - the condition means there is too much iron in my blood and it gets eliminated by drawing a pint of blood every few months.  Recently the doctor ordered that I do it monthly as my iron remains high.  That's the only major change, and I hope that this has something to do with it.

But thank you again - only time will tell.

Hi pigeon and Mina

Thank you so much for your kind words and thoughts - it means a great deal to me.  I also didn't enjoy that comment from the psychologist and, as you say, it's not what one wants to hear!  But the rest of my discussion with him was very valuable and I will see him again on Friday.  

Best wishes to both of you for your ongoing treatment!

Hi scuba

Thank you so much for your reply and for being a great source of knowledge, wisdom and inspiration on this forum.  I also think that it is more likely to be a different bone marrow condition and that was what I was expecting until I saw what the doc had written as her diagnosis.  I'm still hopeful that it is either drug-related or related to my frequent recent blood draws.  Strange to believe I was asking about possible drug reduction less than a month ago!

Today, I received the result of yesterday's blood test and it looks like things have improved ever so slightly:

Red blood cells up from 2.37 to 2.57

Platelets up from 98 to 115

Haemoglobin up from 8.8 to 9.3

White blood cells down from 3.18 to 3.10.

There is no sign of a blast cell percentage anywhere on my report - as An said in a follow-up comment, I also thought that they only report them if they are present and that one assumes they are zero if they're not mentioned.  The comments on the report say "Chromoplasia", "Persistent Macrocytic Anaemia", "Mild thrombocytopenia" and "Leukopenia with low absolute neutrophil count" (the neutrophils are at 1.5).

Thanks again!  I'll let you all know what the diagnosis is when I get the report.

An,you have just saved me from asking a silly question for my nxt blood test....But just for clarification, even when I was first diagnosed , nearly 5 years ago, I have never seen a reference to blast cells. Not even in the early days, when blood was taken every fortnight.

Anyway, thanks again,

pigeon

Hi Sunny,I don't know how it works where you are treated,in my husband's reports,there was one called manual differential,in that they had blast counts.I think you would have known ,so you might be good with no or very little blasts at diagnosis.

Yes An, I would have remembered the term 'manual differential'. Maybe they just don't show it here on the report, or maybe I had very little, as you say. But now I am curious, so when I next talk to my oncologist, I may ask her what was my blast count at diagnosis.

Bloody hell Martin. This must be a serious scare.

I don’t really understand how pancytopenia on it’s own can equate to disease progression. Blast crisis, as we know, generally presents with lots of blasts in peripheral blood.

I know that there are cases of “sudden” blast crisis but this would show up with lots of blasts in the blood work. Here’s some details on that:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555935/

I am hoping that maybe your doctor is inexperienced in some of these matters and this is a case of something much more benign, or maybe even transitory. Have the initial findings been confirmed by a second test? I remember some years back when I had a very scary result but it turned out the machine miscounted, because when the blood was checked under a microscope it was much better looking (blast cells were miscounted by more than a factor of 10).

You should get in touch with Hammersmith Hospital here in London. They offer an “ask the expert” service, and you don’t need to be in the UK or anything like that to use it. It’s offered to both patients and also to other clinicians who may not be CML experts. I know from speaking to them that they would like to see more clinicians get in touch. As I am sure you are aware, they are world leaders there with Hammersmith being the first place in the world to perform a bone marrow transplant.

Here are details of that. There is nothing to stop you asking them about your case - you will get expert advice way beyond what us on this forum can offer. You may also suggest your doctor get in touch with them if they are not a CML specialist themselves. 

https://cmlsupport.org.uk/asktheexpert

Thinking of you … this must be hard to take. Fingers crossed for you.

David.

Hi there David

Many thanks for your reply, for the insightful article and for the really helpful suggestion on getting hold of the Hammersmith Hospital.  I knew that they had the service but thought one had to be in the UK to make use of it!  I'm definitely going to get in touch with them and see what they say.

Thanks also for the crossed fingers.  I can rule out a lab error because I was called back immediately to have a second test, which was done on a different machine, and this confirmed the first result.  So I'm stuck with these low blood counts.

It's hard not to speculate or feel terrified, and I've been trying to inform myself as best as I possibly can before next week.  From everything I've read, it looks like sudden blast crisis is unlikely; however, the most likely explanation seems to be the development of myelodysplastic syndrome as scuba suggested.  I've read several articles that say that it can occur in a tiny population of patients treated with TKIs, and I'm preparing myself for this as the likely outcome.  Nevertheless, I'm holding onto some faint hope that I have because the doctor was wrong before: after 3 years on dasatinib I suddenly developed lymph node swelling that looked to her like lymphoma, but was a late side effect of the drug.  My hope is that somehow my body develops side effects to TKIs late into treatment and that this is just because of the imatinib... and that my counts have suddenly gone haywire because of my frequent blood draws (more than a pint every month).

I just want to reassure people that this seems to be an exceedingly rare complication from all I have read, and that my journey with this condition has been far from normal - my doctor has often described my case as "complicated".  Anyway, I'm grateful for all the advice, thoughts and prayers, and now all there is to do is wait and hope!

Best wishes, and congrats to all in England on the Euro 2022 women's football. I watched the game and was rooting for the Lionesses.

Martin

Martin - I have read your posting and kind replies with much interest.  I went over my previous results and found a blood draw that stood out to me.  For my draw on 3/20/19 (March 20th) I had the following:

Neutrophil Absolute: 1.0 (my lowest ever)

Platelets: 112 (second lowest ever)

RBC: 4.63 (under threshold, happens often)

WBC: 2.9 (lowest ever)

Hoemoglobin: 15 (only one in the normal range)

Coincidentally, or not coincidentally this result is when I had a test go from CCyR to 1.2 on my BCR/ABL.  We switched from Dasatinib to Nilotinib without any mutation testing or BMB.  The following results ever since have been back to normal on all accounts listed above and BCR/ABL in MMR.  My platelets have only been inside normal (above 150) two times in 5 years, currently 141.  If there are no blasts, perhaps a break and switch to another will get the numbers up.  Praying that you find the right solution in the next few weeks.  Keep your head up.

Hi ColoradoGuy

Thank you for your response and for taking the time to look through your blood results for anomalies!  I so appreciate you sharing that experience with me - it's really interesting and shows how the CML journey is full up ups and downs and bumps in the road.  Glad to hear that the change to nilotinib has been a good one for you and that you were spared another BMB - interestingly, the second one was way easier than the first one and I chose no sedation this time.  I'm really hoping that this is, somehow, drug-related and that it's time to switch to something else.

Best wishes

Martin

Martin - Today is the 9th, and I think you were to get answers yesterday?  Thinking of you!

Hi everyone

Thanks for the kind thoughts, Kat, and for checking up on me.  I haven't posted an update yet because it's not 100% certain what has happened to me, but here is the latest from my appointment with the doctor on the 8th.

The good news is that my bone marrow shows normal cells with "no blasts and no malignant cells" according to the doctor, so she has ruled out transformation to blast crisis or AML.  Like Alex and scuba said, it would have been really surprising to go from 0.003% BCR-Abl to blast crisis in less than a month.  

However, scuba seems to have been spot on as usual!  It looks like something has gone wrong in the bone marrow and that I now have MDS at age 44 (surprising, according to the doctor, as most people are over 65 when diagnosed).  This is also consistent with the article An posted, and I am so grateful for all the advice and support of my fellow CMLers.  At the same time, though, this has not been confirmed yet as the doctor is waiting for the result of one final test, which should be out on Friday.  Again, I realise why we are so often called "patients" as patience is so necessary when waiting for results.  The doctor reckons there is a 95% chance it's MDS and a 5% chance that the imatinib is causing the low blood counts, but I have to wait for the result of this last test.  I'm hoping against hope that the long delay is because they can't find conclusive proof that it is MDS.

Nevertheless, it is a really scary time for me because it looks like I'm headed for a bone marrow transplant.  The doctor explained to me that MDS can be kept under control for a few years or so, but that the only cure is to have the transplant and, given I'm 44, this is what we should be aiming for (with the upside that this will get rid of the CML too).  I'm quite shocked that this is now what I'm facing as a month ago everything was so well controlled, but I really want to emphasise to other people on this site that what has happened to me is extremely rare and that it should not be a cause for concern for the vast, vast majority of people, who will live a normal life with a normal life expectancy.  

At the same time it is a reminder that CML can still be a serious disease and that we should live life to the full - I am booked to go on a gorilla safari to Rwanda tomorrow night, and I've decided to go despite this terrifying news, even with these low blood counts.  But life can really bite hard at times because I lost my beautiful Boston Terrier, Domino, to a sudden onset of epilepsy too last week.  This little guy has been my constant companion and support during the CML journey and I've had him since diagnosis.  So I'm still hoping against hope for some good news, given all the bad news I've had in recent times!

I'm going to write an e-mail to the Hammersmith Hospital now giving them this information - thanks again, David.  From what I've read it's not great news when MDS develops from CML as it often has a poor prognosis, so I'm hoping they will give me some information.

I'll start a new thread once I have a definitive diagnosis, but would appreciate any prayers that this turns out to be the medication (I would so much like to try going on 50mg or even 20mg dasatinib, given that I've been in MMR for such a long time).

Best of luck to you all and thank you again!

Martin

Martin, all I can say, my thoughts are with you.

You are really very considerate telling us all not to worry, and that what has happened to you is rare.  True, it is rare, but also true is the fact that this 'rarity' is of no consolation to you. And yet here you are, telling us all not to worry.

Wonderful decision, you going on your safari tomorrow, to watch the gorillas. I am sure the image of a mighty Silverback will stay with you forever. Mighty yet so peaceful (unlike people....).

It really seems sometimes, that we have been singled out for an avalanche of bad news....we look up and ask 'what the hell have I done to deserve it?'     And we never get an answer.....

 I so feel your sorrow about the loss of Domino. Our dogs mean so much to us, and their sojourn on this earth is so brief, seems just like a moment in time, and then they are gone. They always leave us too soon.

After the loss of each of my dogs I would always vow: 'Nevermore'. I just could not possibly go thru this Pain again. But then I always ended up getting another dog. There will be no replacement for Domino, but somewhere, Martin, somewhere there is a little puppy, or a rescue, just waiting for you.

So, dear Martin, go on your safari and know that all of us here are rooting for you. Because we are all aware that, although CML has acquired the reputation of being 'a walk in the park', every now and then it does rear its head with a stark reminder that this Wasp has still got a bloody nasty sting in its tail.

My blessings to you and your dear ones,

pigeon.

 

 

 

 

Hi,

Thanks for the update during a harrowing time for you,go enjoy the safari,the good news is your bone marrow report is normal,I always thought any blood disorders will show up in bone marrow report.
So hope that it might just be imatinib.will be praying for you.

Martin, you are so brave!  Currently, I am not responding to treatment, and I was only diagnosed 9 months ago and am also under the 'average' age of 65 years at diagnosis.  (A lady never tells her age!)  The weird thing is that my doc told me I was in 'great health' at diagnosis and soon we'd be talking sports scores at appointments because I would respond so well to treatment.  I'm still so new at this, and trying to wrap my head around everything.  Trying hard to embrace 'live life to the full' but it's hard when tomorrow seems so uncertain.  I'm not trying to hijack your thread, just wanted you to know that you are an inspiration to me.

I'm praying for you.  <3

Martin - Thanks very much for taking the trouble amidst your distraction to give us an update.  I found myself sinking with the MDS possibility, but then rising with the challenge of a transplant.  Weird!  If that's the best way to go, then you will do it and it will be a success for you.  It just WILL.  They wouldn't keep doing bone marrow transplants if they didn't work brilliantly most of the time.  A hard and scary road, even so.  And unfair.  I'm really hoping you're in the 5% of it NOT being MDS.  Hey, somebody has to be in it, why not you?  Imatinib long-term can do really funny things.  It messed with my creatinine, permanently.  Kind of an ALMOST no harm/no foul situation, but still, nobody can say why it happened to me.  They gave it the old "TKI shrug".

Yes, go see the magnificent gorillas!  Domino's spirit might be there, you never know.  My son was on a tour of Japan with his band, and in a garden in Kyoto he found a bird looking at him and singing to him, and he knew it was my (deceased) mother; it was Grandma.

'K, enuf woo-woo.  Check back in on Friday, please!

Hi,

If possible(and if it is allowed) send the reports also to Hammersmith,because if it is another bone marrow issue,it might reflect in the biopsy result ,scuba /somebody else might know better than me,any markers etc

I'm now probably officially in nag zone - can't stop worrying about your test result from last Friday.  I know you said you would start a new thread when you have a true diagnosis, so please ignore me while you get all your info and your head wrapped around whatever it is.  I can wait!  Sending good vibes.

Hi everyone

First, thank you so much for all the messages of encouragement and for the many kind words about Domino, who was more than just a dog.  Pigeon, I so appreciate your kind words and your understanding about losing a pet - it really means a lot.  Rocky Mountain Gal, thank you so much also for your kindness.  I'm sorry to hear that you are not responding as well as expected and I truly hope that they can get to the bottom of it and find the TKI that is the right "fit" for you.  An, thank you so much for the prayers and the advice!  And kat, I so appreciate your rooting for me and for the regular check-ins.  

I've been quiet because I did my gorilla safari and only got back yesterday - it was a truly magnificent experience and, cliché as it may sound, life-changing to be amongst those peaceful, beautiful creatures in their natural habitat.  However, I found it really difficult tracking the gorillas with my low haemoglobin and at an altitude of 4 800m above sea level.  We were divided into groups depending on fitness levels, and I was put in the "easy" group where I was the only tourist under 65 years of age... and I did the worst of all the hikers, lagging behind and having to rest frequently.  It was very hard to breathe and I developed a kind of altitude sickness that seems to have disappeared now that I'm back home... but it was worth every cent and every short breath!

I haven't got the final results from the doctor yet.  She was supposed to have them on Friday, 12 August and she should phone me in the late afternoon or evening today as she knows I was on my gorilla trip.  In the meantime, though, I've delivered her an urgent letter at the hospital requesting to be switched to either nilotinib or low-dose dasatinib for three weeks before I consent to the bone marrow transplant.  I have discovered an article co-authored by the eminent Australian haematologist Tim Hughes, in which he (and others) describe three cases of people who have developed myelofibrosis while on imatinib.  This spontaneously resolved upon stopping / switching and I am hoping that this will turn out to be the case with me.  I know doctors hate when patients do Google searches, but I know that my doctor holds Prof Hughes in high esteem and that she has consulted with him about my case before, so I'm hoping that she doesn't feel undermined or insulted.  I'm just trying to avoid the transplant if at all possible!

Thanks again, everyone, for the thoughts, prayers, kind words and advice.

Best wishes

Martin

 

Martin, how lovely to hear from you again. Especially with you telling us about the gorilla safari. A 'Life-changing experience' is not a cliche`. It may only sound like a cliche because people tend to describe all sorts of trivialities as 'life-changing experiences'...(like: oh when I met Madonna, it was a life-changing experience....really now).

To see gorillas doing their gorilla things on TV is one thing; to see them actually moving and acting right in front of your eyes is something totally different, which, in my estimation, is worthy of being described as a life-changing moment in time.

Prof Hughes' paper sounds really promising and it brings hope, that stopping the imatinib would resolve the myelofibrosis. Amen.

In fact, your doctor may be rather thankful to be informed about it. Any open-minded doctor should not be irked by their patients being pro-active regarding their own treatment. It is understandable that we do our little researches, instead of just sitting there and accepting everything. At the end of the day, it is our life!

All the best, pigeon.

 

Yay for Google, I say.  I only use the internet to find out things and order things (and write things).  Hoping it's medication-caused!  Keep us informed.

I had altitude sickness, in Alberta, Canada on a family vacation.  It's for real!  We were on a dig and I was just a ghost - no stamina, horrible headache.  Family went canoeing and I stayed under the duvet in my cushy hotel room with a glacier-fed babbling brook outside my window.  That set me right!

Next safari, you'll be motorin' past the first group, you'll see.

 

Hello everyone

Pigeon and kat, thanks so much for your kind replies.  It has been quite a crazy couple of weeks but I finally have some answers.

The doctor phoned me and thanked me for looking for that research - to her surprise, the next generation sequencing test she requested on my bone marrow turned out to be normal, which means that there have been no mutations / additional chromosomal abnormalities!  Those abnormalities that scuba mentioned, such as trisomy 7 and monosomy 8, were undetected, so the only issue with the marrow is that it is scarred.  However, this scarring (myelofibrosis) seems to be "reactive", i.e. it is caused by a toxin (the imatinib) and should be reversible.  So the GREAT news is that, for now, I have been spared a bone marrow transplant!

However, my counts have continued to drop.  Currently I have haemoglobin of 8, neutrophils of 0.5 and platelets of 84.  I have been instructed to stop the imatinib right away for a month, and will receive bi-weekly injections of growth factors in an attempt to stimulate the marrow into producing more blood cells.  The doctor has outlined four possible options upon resuming the TKI.  The first three are what I suggested in my letter: low dose imatinib, low dose dasatinib and regular dose nilotinib; but it seems that the doctor is not too keen on these as she says they all target the same protein and that my immune system is clearly highly sensitive to tyrosine kinase inhibition.  So instead she is investigating the possibility of getting me onto a trial of asciminib, which apparently inhibits a completely different protein.  It will be one of the first trials of this newish drug in South Africa, and the upside is that the drug will be free under these conditions.  But this will all be decided in due course - for now, I'm off all drugs to enable my immune system to recover.  This may even be an enforced attempt at treatment-free remission, given that I've been in MR4 for quite some time!  Either way, the news is much, much better than I could have wished for yesterday.

Once again, I just want to express my gratitude to everyone who responded to me here - for your advice, your kindness, your inspiring words, your thoughts and prayers.  It is amazing to me that people I haven't met have been such a huge support to me during what has been a frightening time, and this forum has helped me so very much.  Of course I have to give a special thank you to my great friend Alex, who nailed it from the start - he has constantly been telling me that it can't be anything other than the TKI and has been a tremendous source of support and kindness.  I am so grateful to this forum for putting me in touch with such incredible people.

I am sure that the trial on asciminib will be of great interest to everyone here, and I will be sure to report on what happens in detail if I am able to go onto this trial.  In the meantime I've breathed a huge sigh of relief and am getting ready to buy some grapefruit!

Thank you once again, everyone.

Best wishes

Martin 

Martin, this is excellent news.

Re: asciminib (Scemblix - Novartis), your doctor is right and this 3rd gen TKI targets the a different site on BCR-ABL: the myristoyl pocket . Trials have shown it is a credible and effective alternative for patients who are resistant/intolerant to 2 other TKIs. However, you should note that asciminib has caused myelosuppression in some patients, so should you have access to this drug you should be monitored carefully for low counts.

https://www.hcp.novartis.com/products/scemblix/ph-cml/mechanism-of-action/

                           !!!FANTASTIC NEWS!!!

No transplant. Martin, you are over the moon of course, and I am sure your great friend Alex is sharing this special time with you.I just came in to turn the computer off, and saw your post, brilliant.

Regarding Asciminib, it is now prescribed here in the UK, and apparently people are happy with the results.

Thanks for letting us know, truth is, we can all do with some Good News for a change....

All the best, pigeon.

 

Hi Martin,

Thanks for keeping us updated,This is such good news,enjoy the forced tfr ,now you can relax and enjoy stress free :)Best wishes on your next asciminib journey,keep us posted

So Good!  I had been praying for you and am very happy to hear of this potential solution that doesn't involve BMT.  Between this and your neck lumps a while back you sure know how to keep everyone worried.  I hope for a quick solution and for you to get back on track as soon as possible.  Thanks for sharing about your trip as well.

Just got back from a little wedding anniversary road trip and checked here first thing this AM (oops, not AM anymore, I guess we partied hard, for old folks).  This is just fantastic news!!!!  I think asciminib is going to be the ticket, and we all get to hear about it.  It's certainly looking good in the trials.  I am just so happy, happy, happy for you that it's not MDS or anything else sinister.  I'm sure your low counts are going to come back up now.  Keep us posted and enjoy this well-earned emotional reprieve.

Thank you so much, everyone!  I'll let you know what happens with my asciminib trial, should I go on the drug.  I so appreciate the kindness of everyone here.  Special thanks to Sandy for all that information regarding asciminib - it looks like a good option, but personally I am more eager to try low-dose dasatinib if the doctor allows it.  In the meantime, I'm looking forward to finding out how I feel off the TKIs for a while... it has been almost 8 years.  Have a good weekend everyone, and thank you again!

HI Martin, just read your post and all the updates. So glad to hear your CML is still well under control, that must have been a miserable few weeks I cant even imagine! I noticed you said you have Hereditary Hemochromatosis. I also have this along with my CML but I am told it is so mild I do not need to have any thereputic phlebotomies. I read about the concerns for uncontrolled HH potentially causing CML advancement and it is always in the back of my mind that I should find someone who takes it more seriously. Basically they say bc my Ferritin and Transferrin are in range they do not care that my saturation % and actual Iron # is high out of range. They basically said watch and wait, I am only 35 and they suggested as I get older I may need phlebotomies but for now not to do anything. I also wonder if your low counts could have been a result of your increased phlebotomies my onc was concerned about supression when I was really pushing to start phlebotomies. If you do not mind me asking how do your HH related #s compare to mine below.

UIBC: 72
Iron: 178
Iron Saturation: 71%
Ferritin, Serum: 293
Transferrin: 199

Hi there John

Thanks for the kind words and for the interesting info - I haven't met many people with HH as well as CML.  Very interesting that you don't need to have the phlebotomies.  My doctor seems far more concerned about the HH than about the CML actually, and I was on monthly therapeutic phlebotomies until my counts started to fall.

To answer your question, my latest numbers are as follows:

Iron saturation : 73%

Ferritin : 491

Transferrin : 153

Unfortunately I don't have numbers for UIBC and Iron.

These were taken before my phlebotomy in July - I skipped August because of the very low blood counts.  My own view is that my phlebotomies have been too frequent.  You're not even allowed to donate blood for 56 days after a donation, so it seems to me that monthly phlebotomies are too often!  Either way, I'm not going to have one done any time soon and I'm going to try to manage the HH with diet.  I'm going to cut out red meat, eggs and beetroot altogether.

Hope this helps a little!

Best wishes

Martin

 

Thanks for the reply! Ya I actually figured out on my own that I had HH from looking at some really old labs with even higher iron and ferritin levels that were taken over 10 years before my CML DX. The doctor never mentioned it to me back then. It is always in the back of my head that I should go see another doctor for it but here in the US its a major hassle. My CML onc does not do anything besides CML/AML so the HH is of no concern/care to her. The two other doctors I saw basically said until my Ferritin is >500 to not do anything. I think these doctors are really just scared to RX a phlebotomy though because of my CML. Also I think they assume I am near end of life anyways bc I lave leukemia and rather not mess with it. It has been over a year since I discovered my HH I actually ordered myself the genetic test to confirm it. I would really like to start doing a phlebotomy every three months with my PCR test but unfortunately I cant just RX myself one :( In your case though I really think the once a month may have been way too much for you let us know how the HH #s and CBC counts do once you get stabilized again :)

Dear Martin 

 

I was wondering how is your health and what is the latest on your treatment? I hope you have got the grasp of your low blood counts. 

PS! I managed to read a post from the past where you informed us of the benign swelling of lymph nodes caused by dasatinib. At that time, your consultant was very certain it was a malignancy (lynphoma) and prepared you for difficult times ahead. In the end it turned out to be a TKI adverse effect. Now your consultant at first wrote "CML transformation" and after this was ruled out, he/she said 95% probability for MDS. 

If this has been the same consultant for all those years, I'd say he or she has a pattern of jumping to negative conclusions prematurely? That is definitely hard for the patient! 

 

Anyways, I hope you are doing well.

 

Timo

Hi Timo

Thank you so much for the message and for the good wishes - I hope you are also doing well.

There isn't much of an update yet because right now I'm waiting for my blood counts to improve.  The doctor expects it to take 3-4 weeks and right now I'm off imatinib and am not taking any CML drugs at all.  Instead, I'm going to the hospital twice a week to have injections of neupogen and epoetin - the first one is to stimulate white cell production and the second one for red cells.  I am feeling okay except that I have some quite bad bone pain in my shoulder, knees and elbow.  According to the nurse who gives me the injections, this is because my bone marrow is being stimulated to produce cells again and I'm hoping it is good news.  My next appointment is on Monday 12.9 and hopefully by then my counts have risen enough that I can start a new drug.

I do feel different in one important way off the imatinib: mentally.  When I was on imatinib, I can best describe my mental state as one of "reluctance".  I was reluctant to do everything: reluctant to get out of bed, reluctant to make food, reluctant to do the housework, reluctant to go to my job and, even, reluctant to go out at night or over the weekend to see friends.  I forced myself to continue but it was always against my will - I just didn't feel like doing anything.  Off the imatinib I feel quite different - even though I don't have a lot of energy because of the anaemia, I feel like doing things, seeing people and even returning back to work.  And I got to eat grapefruit again for the first time in almost 8 years! 

Yes, it is the same consultant that I had with the lymph node swelling!  I know that the conclusions were premature in both cases, but I also look at it as CML patients being very much in the minority, and those who develop side effects like this being even more in the minority!  So, even though it is hard for the patient as you say, I understand her viewpoint because she can't have many patients as complicated as me... and in both cases, it was only the last and final test that ruled out what she suspected.  This is why that facility to ask an expert at the Hammersmith Hospital is so important.  I have the feeling that the patients of most doctors just take their TKIs and respond as expected... so it's the outliers like me that cause a great deal of concern because, I guess, this just isn't supposed to happen!

I will start a new post once I start on whatever drug I'm going to be on - I'm still hoping it will be the asciminib.

Best wishes, also for your ongoing recovery from this crazy condition

Martin