Hello all. Looking for some insight or maybe just a glimmer of light today. So, I was diagnosed ET at 47, progressed to PV at 53 or so. Did Peg, then Besremi for 5 years, but could not tolerate interferon. On Jakafi now for almost a year. Platelets down from 1.1 mill to just over 400,000. But other numbers, wbc, LDH, blasts not looking great. Did a BMB 3 weeks ago. Definitely has progressed to myelofibrosis. But unfortunately, the myeloid panel came back with another mutation ASXL1. This one associated with a poorer prognosis, leads to leukemia etc. Last BMB 2 years ago and showed no signs of this, but as we know this can happen and JAk2 is a driver mutation. (Only I don't like where it is driving me! 😬) At 61, hemo/onco does not feel a SCT is in the cards for me this year. Obviously, we know there is morbidity and risks with SCT. Definitely says I will need one in a few years. Two? Three? Who knows? Have to watch the blasts. Will begin meeting with the Transplant team and testing anyway, just to get on their radar. Does anyone else have this mutation and/or thoughts? Appreciate you all. xx
Not great news :-( ASXL1: Hello all. Looking... - MPN Voice
Not great news :-( ASXL1
So sorry to hear about your progression. I’ve been dealing with ETMF since 2019. I’m on my way to get a transplant in May. I think you should get another opinion regarding a transplant. Did he say what level MF you have? What level fibrosis do you have?
Stage 3. I am glad you are on your way to recovery! Thanks for the advice. 2nd opinions are always good.
So, if you’re stage 3, I would not waste any time seeking out the opinion of an MPN specialist and a transplant doctor. Actually, I’m very surprised that your doctor said you were not a candidate. The younger you are the better.
I do not have ASXL1 but do have the NF1 mutation. It is another of the non-driver mutations that increases risk of progression to AML. So far so good on not progressing. Thankfully, Besremi is working for me.
Wishing you well on your journey.
I agree with Cja1956, you have a good fit to discuss SCT. And your Dr says you definitely require one soon. In some older posts this has been discussed. Current best practice by some specialists for the best prognosis is to do the SCT as soon as it becomes indicated rather that wait for more potential progression where outcome could be impacted. In this thinking there is no advantage, and there may be added risk, by waiting for what you now know is going to be required.
Has your Dr offered a reason to wait? Are there some new therapies Dr wants to try?
Thank you both. Of course, he wants me to remain on Jakafi, but I think the main reason for the wait on the SCT was that he said my blasts were low. He seemed more focused on that than the fibrosis. I will be making an appointment with the SCT team here in Miami and see what they say.
Sorry to hear about your progression. I agree with what other people have said, I was diagnosed with ET in 2009, this then progressed to MF & then MPL & ASXL1 mutations. I was told by 3 consultants that my best option was a SCT, I think you should definitely get a second opinion. However a SCT does come with risks & it does need very careful consideration. I had my SCT in August 2023 & so far I’m doing ok.
Sending best wishes to you & let us know how you get on.
Thank you. I’m calling the transplant team to get an appt. I want to hear their thoughts. I’m glad you’re doing well!!
Agree with Srh55. You seem in a nasty position. You could ask when the docs expect you to be in a position for a sct. If it is only a couple of years why wait? If it was decades it's a different story. I'm 2 years post sct
so sorry for your diagnosis. Just wanted to say my thoughts are with you and I hope you get your SCT soon. Mel x
it’s important to mention although ASXL1 can increase risks it may not lead to Leukaemia.
You don’t say what your LDH or blasts are. Deciding to SCT or not is a big decision with risks and benefits and of course non of us on here is qualified to advise either way.
You are meeting with the transplant team and obviously that’s a good idea. Having observed the path of others in similar position to yours I note they often consult at least several MPN expert haems to get opinions and also several transplant teams before deciding or not deciding.. It’s not black and white for sure. Meds for treating MF are improving and also transplant age limits and success rates are improving.
I hope that helps
LDH 866, blasts at 2% in the blood but 3% in bmb, which is more accurate, I presume. I agree. I think that is what the doctor is thinking. There is a risk with sct and morbidity, as we know. I think they struggle with when to pull the trigger. Poor metaphor, sorry. 😬
I am no expert but as I understand it LDH over 1000 is common/normal in MF, and blasts of 2 or 3 are also not alarming, best check that with a expert or two though.
You are saying exactly what the doctor said Ainslie. Maybe medical school for you? 😂
Hey MiriamMusic... 
Sorry to learn the news of what appears to be some level of progression... From what you report, it does sound quite serious. Blasts are indicative of a shift from Chronic Phase (CP) to Blast Phase (BP). Your numbers may be on a upward trend, I assume...
I am Post ET / MF w/ CALR(2) not JAK2, however, I am also ASXL1+. Also on Rux' but largely fairly stable atm, in my case... I also harbour Von Willebrands Syndrome (VWS), & my Platelets remain stubbornly quite high, (currently 7–800s). Have had a few TIAs (minor brain strokes), & these days have learned to regularly consume daily 'Raw Beetroot Nectar' which is a vasodilator, w/ some anti-platelet properties too... (works for me...) 
I guess some of the decision making by your doctors might depend upon your current symptom-burden vs. your current "Quality of Life"(QL)
How are you travelling in that department? How's your spleen & other symptoms atm?
Your current "Quality of Life" can often be considered as a determining factor when considering the broader picture.
However, taking those first few steps towards preparing for an ASCT now is possibly a wise move too...
My ASXL1, was also originally described as most likely denoting a 'Poorer prognosis' too... However, I'm still hear after my Dx in 2016... I'm 66 shortly...
I did undertake the Tissue Tests (TT) to see if my siblings might be a 10/10 match, they were not, unfortunately... However, at present I 'm quite content to keep muddling through for now... My QL is a tad like a rollercoaster, however, it is manageable for the best part.
I try to manage a healthy 'Anti-Inflammatory' dietary regime, & have taken up cycling some years back now, & generally just try to stay busy...
I can only imagine that you might be feeling a tad overwhelmed atm... That was why I first started chatting here with all the good folk at MPN Voice... All the people here have always proved so helpful & supportive in so many ways...
There are also many others here that have travelled down the ASCT path before you, and whose insights might prove somewhat invaluable to you at some stage...
Please keep us in the loop from time to time...
Very best wishes Miriam...
Steve
(Sydney)
Thank you so much! Yes, I look forward (I think!) to reading about the experiences of others who have undergone SCT. Do they not recommend it for you? As for your questions, my quality of life is pretty good! I am soooo much better off the Besremi. I can't believe I stayed on the interferons for 5 years. I was so sick with GI issues the entire time. I live in Miami, and it is pretty much always sunny, so I am outdoors and engage in exercise frequently. My spleen is only mildly enlarged. I work full time and travel overseas yearly to see family. Lately, people have been saying how good I look! LOL Isn't that ironic? I guess MPN's in general are kind of invisible. Thank you so much for the support!
Yes indeed Miriam, we exist w/ a rather "Invisible Illness" at times... While it's always nice to hear people compliment how good we might look... Appearances can & often are deceptive where we MPNers are concerned...
Stay in touch Miriam... I am sure that some of the ASCT survivors out there will chime in & respond in due course... But if you don't hear anything, pls let me know & I'll try to hook you up w/ a couple I know...
Best wishes
Steve
Hello Miriammusic,
Thank you for sharing your news with our community. I am sending positivity! I do not have that driver but do have Jak2. Hoping Jakafi continues to work, never give up hope as research continues to advance. Hoping the best for you. Hugs DiveGoddess
I was diagnosed with ET, MPL & ASXL1 three years ago (my platelets were high for a long time before my BMB. I am now 72 and doing very well on Pegasys interferon.
Yes, initially the ASXL1 diagnosis also scared me
However my MPN specialist directed me to the studies of Dr. Vannucci a well regarded Italian researcher who found:
"ASXL1 mutations are prognostically significant in PMF (primary MF where MF is the first diagnosis), but not MF following essential thrombocythemia or polycythemia vera"
pubmed.ncbi.nlm.nih.gov/350...
I was also told that 'it is reassuring that ASXL1 is not included in any of the standard molecular prognostic scoring systems for ET, suggesting it's not widely accepted as an adverse prognostic feature for this condition".
As ET was your initial diagnosis perhaps this is pertinent to you too?
Researchers also found that:
ASXL1 isolated mutations (ie, without TP53or high-risk mutations) have no prognostic impact
pubmed.ncbi.nlm.nih.gov/336...
ASXL1-only mutations had no prognostic value, which was supported by the validation cohort.
Sixty percent of cases with TP53 or high-risk gene mutations were associated with ASXL1 mutations and increased the risk of death (HR 1.5; 95% CI, 1.01−2.29; p = 0.044).
High-risk mutations were associated with a higher allele burden of ASXL1 mutations. However, in the ASXL1-only group the allele burden of the ASXL1 mutation was not associated with acute leukemia (p= 0.293) or death (p = 0.763).
I wish you all the best in your decisions on this confusing journey we share.
You have a really good Dr who can connect you to research like this.
Some notes:
-Fig A shows among the driver mutations in PMF and SMF (secondary) each MF type has similar mutation profiles, except MPL was much more prevalent in PMF. It leads to a question, is MPL much less common in ET than in PMF?
-Figs. C (PMF) and D (SMF) show a particular difference in the "Others" (without high risk mutations). TP53 also differed in rate but has very low n. This suggests that, for pts without high risk mutations, if ET does transform to become SMF, SMF is prognostically inferior to PMF, being closer to the prognostic of ASXL pts.
-High risk mutations as were P53, EZH2, CBL, U2AF1, SRSF2, IDH1, IDH2, NRAS, or KRAS" and these were inferior to ASXL while also much less common.
The full reports should have info to give more context to the plots, do you have access to them?
I also have ASXL1 and I'm it's planned that I go to transplant on the 9th April - I'm only 44.
What are your blasts at? What prognostic scoring system are they using for you?
Have you started rux yet? If you respond to rux you may get many years before a transplant.
Wow. I would love to hear about the conditioning you must be going through to prepare! I am wishing you the best of luck. Yes I am on Jakafi and it is working well, keeping my platelets well under control. My blasts are at 2% according to the blood test and 3% according to the BMB. What made them decide to do your SCT now?
PV in partial remision
Secondary PV - Not blood cancer!?!?
Tet2 and inflammation
Sad day...progressed to MF
ET, JAK2, ASXL1 and Besremi
