MPN Voice
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ASXL1 gene detected

Hey guys... :)

Trust you are all coping well with your MPNs, and if you are not... then I hope you will be again shortly... It seems to me that it comes & goes in waves...

In any event, I have just received some interesting news concerning my MPN condition (MF). The results from my recent genetic testing reaffirmed my CALR - type 2 mutation, and also what is referred to as am ASXL1 - Frameshift mutation (which I believe translates as a 'Non-sense' mutation as opposed to a Wild or Random one).

Due to this finding, my specialist now wishes to have tissue sampling commenced in order to match either a Autogenic (sibling) or Allogenic (non-related) Stem Cell Donor. Apparently, at the present in Australia, however, they still might not proceed with the SCT because it might be deemed I am still too well to be made sick...

I shall endeavour to explicate myself...

Firstly, if someone like myself is coping reasonably well with their Quality of Life (QOL), then many doctors are loathe to take the risk of worsening an MPN condition and or symptoms burden.

However, this is a tad contradicting, because if a SCT does become necessary at a later date, (say after turning 60+ yo), then the chances of experiencing a successful procedure are greatly reduced, according to my research.

Nevertheless, this process has now commenced, and if anyone wishes to volunteer any tips in the meantime... please feel free. Your comments will be most welcome of course...

Best wishes all

Steven

(Sydney)

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Sorry to hear This Steve. How long have you had an MPN? Did you have pv before progressing to MF. I'd be pushing to have the stem cell transplant as soon as possible. Next thing they might be saying you're too old . I'm 74 with no problems luckily yet . Pv dx 4 years ago - on hydrea and aspirin. A few people have had SCT 'S in Australia. Are you on MPN Australia site ? Lots of help there. Marion

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Hey Marion... :)

No, I was actually originally diagnosed as ET (2016), but short-lived, as soon as BMB results returned they reclassified to MF... Hence, I might have been MF from the start? I actually MPN Voice for more helpful but our Ozzie sites are slowly permeating through the cracks, or so I hope...

Best Marion & thanks for your support too...

Steve

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Steve here is its name- It's called MPN AUSTRALIA and NEW ZEALAND Support Community.

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Hi Marion,

Is it on Facebook or a separate website and if so what is the web address, I live in New Zealand?

Wendy

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Hi Marion,

I found it on Facebook and have requested to join the group :-) There are only four of us on her from NZ that I know about so finding others would be good ;-)

Thank you!

Wendy

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Oh that’s good - lots of conversation on there and advice.

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Hi Steve,

I’m really sorry to hear of this latest development in your MPN journey. It is a very difficult decision for both you and your haematology team with regards to ‘the right time’ for a SCT.

If I have learned one thing about you, it is that you are well researched on your condition - and that will give you confidence. We’re all here to offer you the support that you need.

I truly extend my sympathy, and I’m sure the two Chris’ will offer their expert advice on the SCT side of things.

Thoughts are with you

Mary xx

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Hey Mary... :)

Not so glum... I half expected this result, as I have been having a tad of a roller-coaster ride thus far...

Thanks for your compassion and support. That is precisely why this MPN site is the very bset things available globally, in my view...

Cheers

Steve

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Sooo many typos... sorry guys... :-(

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Perhaps one question to ask is whether any imminent breakthroughs re SCT and especially re Graft v Host? I posted a link on encouraging Graft Host trial result a month or so ago.

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Hey Paul... :)

Definitely worth looking into further Paul, and thank you for the reminder. I shall look for your previous link.

Part of the problem in Oz is simply that there are not too many doctors/specialist that deal exclusively with MPNs. Hence, options are somewhat more limited than say in the UK & especially the US where volume assists in the economics etc...

How we humans all come to our varied perspectives is quite a fascination really, but simple in the end, (it's just economics), in my view.

I have just helped a buddy of mine locate a Bullbar for his 2005 model Range Rover Vogue. That particular model was the last of the BMW components prior to Ford taking over, and in Australia, there are very few 2005 model Vogue Range Rovers. I did eventually locate a Bullbar manufacturer/Installer located in Queensland, and as we are based in Sydney, it meant driving the vehicle there (c. 2,400km round trip), and paying a premium to have those works completed. Alternatively, there was one other group that could do the work, however, that was a drive to Perth in WA (c. 8,000km return), and if they could not use their existing licenced template, then a 'Crash Test' would be necessitated & undertaken (@ an extra $AU8-10k). Naturally, my friend chose to take a drive to sunny Queensland, and besides for him, money is not at issue... :)

Fortunately, metaphors aside, I do have two potential autogenic donors in my younger sister & brother. However, as some others have mentioned in medical journals; allogenic donors are fine too provided they are a 100% match. Unfortunately, and as we are all aware, the randomness of life is ubiquitous to say the least. Nevertheless, I will be intrigued to learn more from the GVHD breakthrough literature you mention.

Much appreciated Paul

Best wishes

Steve

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Steven

I wish you well my friend. My PV has turned to MF so i will be travelling down the same road but i am 64. By the way I also live in Sydney

Garry

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Hey Garry...

I appreciate your support of course. Maybe we should organise a cafe catch up sometime...(?) I can be reasonably flexible Garry. I will send you a private message with my details shortly.

Best wishes

Steven

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Good idea for you two in Sydney. My mate Danny and I rode shotgun on each other as we went through SCT. Me first, then him. Although I met him online he only lived a mile away.

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Cool... Great idea Chris... :)

Having a buddy for this sounds logical.

Let me know what you think Garry...

Cheers

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Good luck Steven

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Cheers... Wyebird :)

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This is a difficult question that I have answered in various ways over the past seven years. We all know that ultimately MF has an unpleasant outcome although it can move slowly for many years but can also speed up; the course of the disease is not predictable. This can be helped by recent drugs that help with the symptoms of the disease but do not stop its progression, (although how much they will ultimately offer is not known). Transplant (SCT) is the only current curative option but can also kill. Not everyone can even have an SCT as they might have co-morbidities or generally not be healthy enough.

I made my decision to seek a potential SCT as soon as I knew that I had MF as I didn’t like what was going on inside me. A few months of appointments with a haematologist who viewed SCT as unproven, I went for a second opinion consult with the brilliant Dr (now Proff’) Claire Harrison. I was told that I was confirmed as IR2, would need to have SCT within three years and appeared to be a suitable candidate. I chose to pursue SCT immediately. Jakafi (Rux’) was not available as was still in trials, so not a complication for me. However, I am not sure it would have made any difference to me going ahead.

What I was told by Claire, and the transplant team she sent me to at a different hospital, was that 20% do not survive the process. 20% could revert to MF, 60% are okay after 5 years. My HGB was 8.1 and becoming transfusion dependent (which I never did) was seen as a negative factor. I had to have Heart, Liver and Kidneys tested to make sure my body could put up with the rigours of SCT. I passed and here I am today. It is not an easy road and process but it is worth it.

The other question is GVHD. There is no telling/indication prior to SCT how this will be, post SCT. Some have a relatively light outcome and others very tough. I had chemo related gout for a while, abdominal discomfort on and off for a couple of years and no end of tests that discovered precisely nothing wrong! My hearing is worse and I have a bit of memory related chemo brain. However, I still travel, Kayak and run (8 miles this morning). One of my transplant friends, Genny, is six years out and still has a very tough time with GVHD but is still able to be a yoga coach. Others are fine.

So my view is go for it when you are fit enough to put your body through it and don’t leave it until you are too ill to deal with it. As for GVHD, its better than not ever having had the chance to have it.

ps There is a group of top MPN specialists from USA, UK and Germany (and possibly some other countries), prompted and co-ordinated by Zhenya Senyak (a lovely man who has MF, is too old for SCT but is driving the work as he lost two friends who went into SCT too late and died) currently debating how to work out an algorithm to help decide when someone with an MPN should go to SCT so that it is not too early or too late. It will take a lot of work to determine this but should be good for the future.

Chris - the transsexual transplantee (thank you Sarah Gardner my donor)

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Thanks again Chris...

I do enjoy learning from you & your experiences. A new algorithm would be most useful...

The discovery of the ASXL1 gene, in combination w/ others, also produces some prognostic values but still just an approximation, and obviously it will still vary from case to case etc...

I am definitely leaning towards the logic of your suggestions, however, it is a process, and I am just at the first stages of this exercise. I will know more after next week's tissue samples have been collected.

Chris was your donor allogenic or a sibling, if you do not mind my asking?

Steve

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SCTs for Myelofibrosis are allogeneic be they sibling or MUD (Matched Unrelated Donor). My transplant was MUD as I didn’t match my two sisters. Sibling match is about 1 in 4.

Autogeneic(aka Autologous) Transplants use one’s own stem cells and are used for conditions like Myeloma. Skiing this year on a table of six in a chalet of 40, I ended up sitting next a myeloma SCTer who had his transplant 16 years ago.

You can ask any question you like I try not to push anyone to transplant but provide information to help their decision; it’s not an easy one to make especially when still well.

Chris

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MUD... We do have some wonderful acronyms do we not?

Defined as: soft, sticky matter resulting from the mixing of earth and water.

However, thank you once more for the clarification of the donors. :)

It is such a small world at times... I recently had an interesting trip to Fiji that highlighted the so-called 'Six degrees of separation'. Longer story later perhaps... :)

Incidentally, I have now spoken to Garry via mobile (Garry is the other guy from Sydney w/ MF), and he is also based in Sydney, and seeing a SCT specialist that I will ask my GP for a referral to. I will endeavour to explore and seek as many opinions as I might concerning SCTs.

It is not that I doubt you at all Chris, in fact quite the contrary. It's just that Australia at the present is not yet as progressive w/ MPNs as say the UK & US. Many GPs, & even specialists are still only just learning about the existence of MPNs... My English GP is the first to admit he knew very little of MPNs until I walked through his door. These days he thanks me for his MPN education... :)

Chris did you also have a gene test undertaken to learn if ASXL1 was present in your genetics & vascular biology?

Best

Steve

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Never felt you doubted me was just trying to soften my last comment that offered my opinion. There are times, like buddy no 1 whose blasts jumped to 20%, that JFDI applies, and she’s good after six years. There are others where watch and wait for a while, like Danny got married and became a father before going ahead. I don’t think that gene knowledge was available then, only JAK2 ever mentioned and then in passing. They are learning all the time

Chris

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True... :)

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Thanks Chris

In terms of prognosis, you quoted Claire at 20%/20%/60% but this was well over 5 years ago?

Do you have any view on current odds? From what I’ve read there have been significant treatment advances?

Best

Paul

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Not really Paul. I have had 70-100 buddies in the last 6.5 years with some just a couple of calls to help them understand their condition, options and to translate some of the medical blurb that arrives thick and fast in understandably short doctors appointments at the beginning. There are others who are now friends. I have lost several too but have never kept count.

A german doctor who presented at Claire Harrisins patients day 3/4 years ago claimed 85% success.

There are so many different hospitals in various countries that I think stats would be difficult.

I am going to a transplantees survival symposium in Denver at the end of the month. There are normally 400+ at these and to give you an idea of our rarity there were 8 mf-ers at the first one I went to and three at the second!

There are two sessions of ask the transplant doctors and I will ask them and report back.

Chris

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Love to the fly on the wall... 3 MFers ... so very rare...

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To be the fly on the wall... sorry brain fog... :-[

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Hello Chris,

Just a couple of points:

When can you be considered as a 'transplantee survivor' - I had my SCT just over 30 months ago and most 'unpleasant stuff' is behind me so perhaps I'm a survivor now?

You state that MF-ers are rare, how about MF +MDS-u 'ers?

I agree that the 'dilema' "SCT early when in 'good health" or "sit, wait to see what happens" is not easy. For me it all depends on the advice of the professionals around you and on your personal conviction.

Bye for now

Gary

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Ah, newbie! 😀 Even getting through SCT is being a survivor although the medical target normally mentioned seems to be five years. 30 months is excellent!

There are a lot of MF SCTers but it is a small number compared to other conditions just like getting MF is so rare in the first place.

Strangely enough I went to Northampton yesterday to meet a new buddy from Leicester whose dad (mid 60’s) has Myelofibrosis and MDS and is weighing up SCT. He is discussing with experts and haematology say no while the transplant team say yes! An interesting dilemma. Might need some help/info from you if he goes ahead

Keep on pushing up the averages, Gary

Chris

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Interesting exchange between haemo and transplant teams - in my case it was more the haemo team saying to the transplant team 'we have a client for you'.

Following advice from the haemo doctor I got a second opinion from another specialist in Paris (JJK) who confirmed that a SCT was the most suitable option for me. After the transplant team explained to me the potential pitfalls that could arise with a SCT I went back to the haemo to 'confirm' if this really was the best option - even if deep-down I knew it was - and then went back to the transplant team.

Follow up and weaning off of my treatment (pegasys) before transplant was done by the haemo side of the team.

Always at hand to give a helping hand if it can help.

Regards

Gary

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A couple of questions if I may that might help with my new friend. What age were you going in and had you had any transfusions?

Chris

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I had my SCT when 53yrs old (diagnosed a year earlier).

Whilst under treatment with Pegasys I had no transfusions ( although my counts were very low and followed on a weekly basis); however when I stopped Pegasys to prepare for the SCT I fell rather ill and my wife told me I had received several red and white transfusions. I must admit I was in a sorry state and didn't really know what was going on.

Nb:This was before the SCT and not due to the SCT.

Take care

Gary

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My husband had MF/MDS and had a SCT aged 67. That was 4 years ago. He was very poorly at one stage and has ended up dialysis dependant, but has otherwise a good quality of life.

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Hey Gary... :)

Thank you for your input.

It is a dilemma is it not?

I will be seeing my GP this afternoon where I will explain why I believe I need a further evaluation from another specialist.

My current specialist is a very good doctor & has a wonderful bedside manner. However, MPNs are a relatively new frontier, and I often feel like I run a poor second to those w/ tumour type cancers.

Just recently, my specialist said something quite odd, when they mentioned my latest gene test results. For my specialist had forgotten that one of those results was already a known factor, which proved to me that my doctor had simply forgotten that rather salient point - (CALR+ Type2).

One might be forgiven, knowing just how busy our doctors can be...

However, as I recall, it was me that had to push to discover the CALR, and it was also me that had to push & explain again, why learning if the ASXL1 mutation was present, because it can have some prognostic significance. Hence, I have now lost faith in my specialist & need to find one who actually remembers me...

The decision to undertake SCT or not is tough enough. However, I believe that the sooner one attempts this the better the odds, generally speaking of course...

Thanks Gary

Best wishes to you also

Steve

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Hi Steve,

I was lucky to have fallen ill in a city with a hospital with specialists in blood cancer/transplant. Although my GP messed up completely in the phase leading up to my diagnosis a family friend doctor took a look, discussed with him and then recognising his potential error fast tracked my to the hospital specialists.

Pretty early in proceedings the SCT was identified as the way to go, "your young, healthy - it should maximise your chances"- was something I frequently heard.

One specialist (I saw 3) did suggest waiting which threw me a little.

I know the decision is delicate - we don't have a crystal ball to make the choice easier.

Good luck with your decision.

Gary

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Cheers Gary... :)

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Hello,

I recently learned I also have this mutation based on new testing from the MPN specialist. I believe the qualifying description was "missense". I have ET so I have to be followed closely, every 3 months.

I do agree on the SCT, needs to be made available sooner.

Take good care.

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Hey Indigo... :)

Interesting. Yes, Missense, Non-sense, & Frameshift mutations are all a tad different from one another, as I understand things thus far.

My mutation is a Frameshift mutation. Apparently, depending upon the various compositions of mutations, some have greater Overall Survival (OS) than others.

As I am also CALR type2+, and now ASXL1+ too...

The jury is still out as far as my own research is concerned. I am still in the gleaning process, however, the only conclusion I can draw at the present is... Not to draw any conclusions!

Best wishes

Steve

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I wish you the best, I know learning that one is positive for ASXL1 is difficult to hear. And of course the SCT dilemma is also difficult, as it is certainly risky.

It seems if they can find some remedies for GVHD, this would improve outcomes drastically.

I am hopeful better drugs options are on the horizon.

Take good care.

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I shall keep you & everyone at MPN Voice appraised as things move slowly forward...

Steve

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Hello Steve,

The Royal Hospital in Melbourne has a Professor Ritchie there who is head of the Bone Marrow Transplant team I believe he has really good knowledge on MPDs .maybe you can get some good information from them. Bye Gill

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Hi Gill (and apologies to Steve for going slightly off topic),

Last year a young Melbournite wrote a beautiful blog as he went through a successful MUD transplant for myelofibrosis. dnewman80.wixsite.com/mfandme

No matter their age, we parents can not help but have 'what if' moments for our kids. Hopefully your son will stay well for a long time and the MPN world will be quite different. Still, it is nice to know there has been success in Melbourne when having those 'what if' thoughts.

To Steve, liked you 'wave' metaphor. Even though you know there are rogue ones out there it is disconcerting when one sneaks up on you and knocks you off balance. Best wishes, Simon

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Hello Simon, Thank you for that. Its eleven years now since his PMF diagnosis thankfully he is really well. Its hard when he is so far away. Bye Gill

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Hi Gill... :)

Thank s for the heads up. However, I might try Garry's guys first at Sydney's RNS because that is a lot closer to me than Melbourne is. I will just take it all a step at a time & see where it all leads me etc...

Cheers

Steve

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