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At an early crossroads, would love your thoughts

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Six months ago (Oct 2018) I was diagnosed with accelerated CML (33k wbc, 13% blasts, BCR/ABL 44%). Fish showed positive for t(9;22). 

(Unfortunately, and probably not coincidentally, at the same time I had pericarditis with tamponade, requiring emergency surgery and a week in the hosptial. This was followed by several months on amiodorone, colchsine, dialtizem, and prednisone. I do strongly feel these issues and medications complicated my subsequent CML treatment.)

Once released for the pericarditis, I went on 140mg of Sprycel for about 3.5 weeks (10/9-11/1) until my blood counts bottomed out. First the platelets, then the neutrophils.

So for 4 weeks I was off Sprycel. Then for 1 week (11/30-12/6) I went back on at a lower dose, 100mg, but quickly saw low blood counts and stopped right away.

When my numbers hadn't come back up soon enough after 2.5 weeks, my doctor took another biopsy. The best news was that blasts were now only 1%. But it also revealed a new metaphase t(8;21). Concerned about the meaning of this and next steps, he sent me to see a colleague in the same organization. This doctor said the new metaphase likely resulted from being off treatment for so long. (Oh, he also ordered a fish test, which was negative for AML... huge relief.) But based on the clonal evolution, he was rightly concerned about letting me reach acute/blast phase. 

So on 1/7 I was basically placed on a 3 month ultimatum. Either fix this with chemo or do a bone marrow transplant. I was entered into their bone marrow transplant program and they already found 4 donors who are 10/10 matches--a welcome bit of good luck, even though I'd rather avoid needing their help.

The chosen path was a lower dose of Sprycel and hope that things improved while my body tolerated the chemo. (If things got too low, he said they'll give me nupegen. Potentially I'd switch to Bosutinib.)

Accordingly, I restarted Sprycel on 1/7. The dose was 70mg every other day since I had those pills on hand. After 2 weeks, it went down to 50mg every other day, which is the dose I'm on right now.

Unfortunately, today my blood counts are crazy low: neutrophils 0.15 x10(9)/L; platelets 29 x10(9)/L. Despite this, my team still want to continue at 50mg every other day, obviously in hopes of avoiding any leukemic setback that would force the bone marrow transplant. 

For reasons that became obvious to me with more information, I hope to manage the CML with chemo. This motivates me to stay on Sprycel despite the terrible cell counts. But I'm also worried about the cell counts, and worried about taking nupegen, and worried about anything that doesn't help. 

Oh, I should give you my BCR/ABL counts: 9/24--48% (before Sprycel); 10/5--44% (still before Sprycel); 1/7--40% (11 weeks after last Sprycel, which had totalled only about 4.5 weeks); 1/10--50% (after a couple of days at 70mg every other day); 2/8--27% (after about 5.5 weeks on 70mg and then 50 mg every other day).

Right now I mostly wonder how to approach my current low cell counts against the strong pressure to keep fighting my leukemia, considering my clonal evolution. I don't want to let up on treatment but I don't like how low those cell counts are. And I hope to avoid a BMT. What to do? 

Thanks so much to this amazing community, and thanks for any thoughts. 

Hi Bill,

Sorry to hear about your situation.  It sounds like you're on the right track with your treatment.  It may just need some fine tuning and a lot of patience as you continue your battle.

Scuba also had a rough go when he started treatment.  His treatment was similar to yours early on.  You might be encouraged by reading about his treatment history here: http://cmlc.ml/  The number of posts he has written over the years is prodigious and hopefully will be of some help to you.  http://cmlc.ml/community.lls.org/topic/4416-just-took-my-first-gleevec-p...

Many of us had low vitamin D levels.  If you haven't looked into that, it might be beneficial to research that.

You could also post a query here: https://communityview.lls.org/groups/chronic-myeloid-leukemia.

Welcome to the CML Support forum!

Kirk

 

Kirk - Reading Bill's account was like deju vu - been there and through that.

Bill - You can read through previous posts of mine using Kirk's links so I won't recount here.

What I will summarize is you can get through this without neupogen (strongly discourage this) and without a bone marrow transplant. I also had clonal abnormalities - AML indicating to be precise which was a big concern. But my doctor said he saw this all of the time in newly diagnosed patients. My myelosuppression was very severe - dangerously low. What my doctor did and what I did on my own together enabled me to manage through the low counts (pulse treatment), eliminate blasts (which buys you time to manage the low counts) and ultimately lower my dose of sprycel to 20 mg a day (no side effects I feel) and I am "undetected" today. The first 18 months are the toughest.

Summary:

1. Get your vitamin D blood level up to over 50 ng/ml and keep around 70 ng/ml (I take 15,000 IU's over two days in winter, 5,000 per day in summer). Everyone is different so test. You will be surprised at how low your vitamin D level is currently. Vitamin D helps drive blasts to differentiate and disappear including leukemic blasts.

2. Consider taking Curcumin (8 grams per day with piperine (i.e. pepper)). Curcumin slows down CML - again buys you time.

3. Neupogen STIMULATES the cancer! I would never take it - especially when blasts are an issue - see link below:

http://ar.iiarjournals.org/content/34/11/6747.full

My doctor very much wanted to avoid me taking Neupogen (he already knew of the issues) and preferred I stop treatment to allow counts to rise and then resume treatment at lower dose. I had to do this 5 or six times. On - then off - on at lower dose then off ..... As long as your blast count is below 2-3% even higher you can get away with this. My neutrophils fell below 0.1 (or 100 depending on your scale). I would go off drug to let neutrophils rise to above 0.7 and then resume sprycel - first at 70 mg and then ultimately 20 mg. I was never started at 100mg.

4. Sprycel should be taken every day when resuming. CBC (blood counts should be tested once per week until stable).

5. You want to take the lowest dose possible that works that does not cause severe myelosuppression. In the case of sprycel - more is not better. You want to find the correct dose for you that trends your PCR (FISH) downward. Sprycel half-life is 5 hours. This is why it is vital you take it every day instead of every other day. But only take it when your blood counts are high so you can take it every day. When you hit CML - you want to hit consistently - then stop if you have to - you are allowing your normal system to pulse upward while your leukemic system is pulsing downward.

Over time you will find that your myelosuppression will be less and less each cycle. Your clonal variations will likely disappear (mine did after the first few cycles). And assuming vitamin D is rising (takes months for that to occur), your blasts should stay low and ultimately disappear as well.

Work closely with your doctor and share with him/her your thinking based on what you have read here. If he disagrees ask why. Most doctors have no knowledge regarding vitamin D and curcumin.

You'll get there. It will take time. Armed with knowledge and a good oncologist, you work the problem together.

Best

 

Thanks Kirk. It’s such a help to be surrounded by others who understand what it’s like having this disease. And so remarkable to read Scubas story. I too had pneumonia (and pleurisy) a year before diagnosis. Unfortunately my blood wasn’t tested then, and it wasn’t until I had heart rhythm issues almost a year later, which culminated in pericarditis, that my white cells were measured and set diagnosis and treatment into motion. I have a lot of homework to and am so grateful for the generosity of this community : )

Scuba, wow, I must've been typing while you submitted this. It's really crazy the similarities. I too was told that my new translocation normally indicates AML (the fish test for AML showed no fusion and thus was negative). But that new translocation was how I got put on track for a BMT, and really upped the urgency of my treatment. Right now, it sounds like my blood counts are pretty close yours when they bottomed out. Yesterday my neutrophils were 150. My previous record low was 170. And like you, I also had cardiac events shortly before diagnosis... tachycardia, then a-fib and a-flutter, and finally acute pericarditis and tamponade. I was 30 minutes from lights out. All of this, along with my CML diagnosis, came about a month before my 48th birthday. Which is to say that I'm encouraged by your story, though have some major hurdles to clear before I start feeling comfortable. Can I ask... if April comes and my doctors advise a BMT, can I challenge them? Can I ask for more time to let the chemo work things down? How does a conversation like this go? Hopefully they see the progress they want to see, whatever that threshold is, and I don't have to have that conversation. But maybe they won't. I can already see that my primary Hem-Onc doctor wasn't as familiar with these clonal abnormalities as yours was. My reasons for wanting to avoid the BMT are mostly the obvious medical ones. And too, I would have to move to Rochester for 3 months. I've got a wife and two young kids here at home. It would be very hard on my whole family. Who knows what condition I would come back in. And yet I don't even know how to tell a Hematologist at Mayo Clinic that I question their treatment plan. Thanks again for sharing your knowledge and experience. 

Scuba

You mention you take 8 grams a day of Curcumin, I have looked for some online but can seem to find any that come in similar doses/tablets. I can find some that are 500mg?? Quite confused about this.

Also so it says that Curcumin helps reduce blood clotting. As my platelet count is on the low side at the moment would I still be ok to take Curcumin or would this just make it worse?

Sometimes when you go looking - you find. That is how I learned about clonal populations of cells that together define blood abnormalities - the worst of which lead to CML, AML and related. We generate "abnormal" cells all of the time - often in sufficient number that show up in tests. But if we are not looking - we don't see them. When we were diagnosed with CML, our doctors are "looking". And sure enough they found.

In my case, I had two clonal variations in addition to CML - monosomy 7 (an indicator of AML - very bad) and trisomy 8 (thought to be benign). Both of these showed up AFTER my CML started to decrease. Chances are they were always present, but masked by the enormous population of CML cells. As CML was brought under control, monosomy 7 became pronounced and then disappeared. I'm glad it did. I still live with trisomy 8, however. it rises and falls, but I still have it. I don't know why. I suspect that it is the reason why I am still anemic even though I am PCRU and only take 20 mg Sprycel. Some real damage has been done to my bone marrow (I suspect CT-scans). I take Curcumin and maintain vitamin D in order to increase my odds I will live out my life. My mother is 97. And she is tough.

My primary hematologist had no idea what to do except protocol in my early days ... i.e. increase dose. I  sought out a research oncologist, one of four in the world on CML (Dr. Druker being number one) and that is what led me to success. That is what I share with this forum.

Diane - I took 8 grams when I was at my worst with CML. Anyone with a lot of blasts should take 8 grams of Curcumin ( in my opinion). I don't take 8 grams a day anymore (it's expensive otherwise I would !) - instead I take two - four. It comes in one gram caplets with piperine. So I take a few per day.

My wife takes it too now - but for its anti-inflammatory benefits. It's great for arthritis and the mind. Search for Curcumin C3 complex. That's what I take.

 

Vitamin D interests me on many levels. About three years before my diagnosis I was having a lot of trouble with heart rhythm. I saw my primary physician, who tested me for Vitamin D and gave me a little paper he wrote explaining how he felt everyone’s D levels were slowly eroding, but especially in northern climates like the one I live in. He saw a lot of farmers in his practice, and noticed that yes, they would get skin cancer. But it wouldn’t kill them. He said these folks died instead from the Western Diet, mainly heart disease. He not only advised getting more unprotected sun, but even suggested going to a tanning booth in the winter months. So he had a pretty established viewpoint on D and saw a possible connection to it and my heart rhythm issues. So my count at the time came back at 16, which he said was pretty low. He had me take 10000 IU/ day for a month, and then to take those calcium chews that have 1000 IU of D3 2x/day—so a maintenance level of 2000 IU/day. He said it can take up to a year to start getting the benefits of having appropriate D levels. I followed his advice through the winter but then inexplicably stopped when summer came. For the next couple of years I was very sporadic at taking those chews, which I now regret. I haven’t had my D levels tested since back then. I’m certain that my CML was already in the works at the time, and probably had been for years before that. Just a bunch of random little cues, strange new bodily responses to various stresses that previously had no effect. For the past several weeks now I’ve been taking a K2+D3 pill along with Calcium Citrate.  I’m getting 5000 IU/day of the D3. I read that the K2, D3 and Calcium are interrelated (along with magnesium and who knows what else). I’ve asked my oncologist to include a D test in my next CBC. Haven’t heard back but I doubt my levels are anywhere near 30, and unfortunately may have even slipped back under the 20 threshold. 

Bill - I suspect just from reading your post that your D levels are probably in the so-called normal zone (20-50). Vitamin D level below 20, one has to not take any supplements whatsoever and avoid the sun. It does take months to build up D levels, but also months for D to deplete. It is noteworthy that the timing of D increase and decrease correlates roughly to the sun exposure from winter to summer. Maybe nature knows something we don't - or a better explanation is we evolved to take advantage of the sun when it is high in the sky storing up D for use in the winter months when it is low in the sky. And over the equator, we evolved dark skin to shield from the sun all year round. Dark skinned people have a much tougher time getting adequate vitamin D from the sun - except those around the equator.

Supplements are very useful - but only to a point. Getting sun exposure in order to convert cholesterol in our skin to vitamin D active form is the best way to get proper levels. It's just hard to do.

Strive to get your D level up above 50 and keep it less than 100 (which is easy to do as long as you stay at or below 10,000 IU's per day). I personally would never take calcium supplements. As long as you eat veggies (broccoli) and any dairy (cheese), you are getting plenty of calcium. It's abundant in our food unlike magnesium which is not. Taking vitamin D + calcium just causes calcium spikes in the blood which is hard on the kidneys and can lead to calcium deposits in the arteries (and soft tissue). Of course, by taking K2, you minimize that impact as K2 moves calcium to the bone and together with vitamin D deposits excess calcium there.

 

Thanks Scuba, that’s the nudge I needed to stop taking calcium. I don’t have a ton of dairy but probably get plenty elsewhere. Unfortunately I do tick most of the boxes for vitamin D deficiency—olive skin, live in upper Midwest, work inside, even live in a shady area. When I started Sprycel last October my oncology nurse said I need to stay out of the sun or use high index sunscreen. It sounds like you don’t think that’s necessary?

I'll never put on sunscreen again.

The irony and paradox is that vitamin D protects you from the sun potentially protecting from skin cancer, but it takes the sun to produce vitamin D.

Gradual exposure as winter gives way to spring and summer was the way of our ancestors. So protection built up as the seasons changed. Today, we stay indoors losing our vitamin D and then suddenly - around June 21st, (northern hemisphere), we jump outside for our vacation in the sun and burn up. No vitamin D to protect us and we get skin cancers. What a surprise.

It's almost March in a few days. I am already starting to get some sun at noon. Step away from the computer and get outside. Unless it's raining.

 

So after all of the above, last week my doctor took me off Sprycel. I had been taking 70mg and then 50mg every other day from 1/7 until 2/27. During that stretch my BCR/ABL has really jumped around...

10/5: Dx with CML 
10/9--11/1: Sprycel 140mg
11/2--11/29: off 
11/30--12/6: Sprycel 100mg
12/7--1/6: off 
1/7--2/4: Sprycel 70mg every other day
2/6--2/27: Sprycel 50mg every other day
3/1--present: off

9/24: 48%
10/5: 44%
1/7: 40%
1/10: 51%
2/8: 27%
3/1: 36%

What's interesting is the 1/7 (40%) results came after 5 weeks OFF Sprycel, and the 1/10 results (51%) came after a couple days back on it. These are all coming from blood tests. What is the significance of so much disparity? 

This is so frustrating. 

Bill - So very sorry you have encountered such rough seas.  I am not qualified to speak to the heart issues.  But I can tell you two things:  Your PCR's are all pretty much grouped in the same range, and I don't believe statistically the variations are significant.  Doing two PCR's in one day could yield similar disparities. 

The second thing I can tell you is, you have not been on Sprycel - or any TKI - long enough to tell ANYTHING.  Many of us, particularly some of us who were diagnosed 10 years ago, were not alerted to myelosuppression and we just went along with the doctors, who in turn didn't share all the details of our out-of-whack CBC's.  The knowledge about our "numbers" is a double-edge sword.  It's impossible to un-know low ANC, low platelets, etc. and yet, many of us had those numbers for months and months, unwittingly and to no ill effect.  Eventually, they evened out and came back up.  I say this not to belittle your situation or suggest that you not keep on top of things, but only to encourage you to consider that there likely will be improvement and that myelosuppression is completely "normal" for us in the initial treatment phase. Barring more information that would indicate for a transplant, I would say that you haven't anywhere near exhausted the TKI options.  You've really not even barely started.  

Are you sure that you are being seen by a CML specialist and not a transplant center?

Bill - I echo Kat's note to you.

I had similar PCR's to you and had to be on and off sprycel. But what my doctor did was put me on a low dose (20 mg) to let it work longer before myelosuppression set in. As long as your blast cell count is zero or a few percent, you can continue this way - on again off again as your body re-develops its normal blood system and acclimates to sprycel. It took me several cycles until my myelosuppression stabilized - I was able to stay on drug longer and longer and then I was good to stay on.

The good news - I just stayed at 20 mg and my PCR plummeted. Less may be better in cases of myelosuppression.

Kat:

Thank you very much for that encouraging reply. I mildly freaked out last January when my doctor said "Let's try low dose Sprycel for 3 months and then see if you get better or need a transplant". That's obviously a paraphrase, but it's a pretty good summation. My next appointment after that one, a week later in mid January, was with a transplant specialist. So when the 3 month mark rolls around, I'm not sure what their view of 'better' will be. I don't know what makes them think "drop everything and do a transplant." But in natural conversation, it felt like a very narrow window. So knowing that that my PCR numbers alone *so far* are probably statistically inconclusive is very helpful.

And no it wasn't even slightly belittling. I love context. I'm a huge context guy. Knowing what you and others experienced before the current protocol opens a whole new world of understanding for me. 

Regarding my doctor, I'm in the Mayo health system. My primary and local Hem-Onc, whom I still see and really like, is probably not a CML specialist. I honestly don't know. I doubt this particular facility could have someone who focuses on leukemia, although I could be wrong there. Last December he did refer me to Rochester, which is obviously a huge facility, and where I saw a Hematologist who specializes in CML and AML. This 2nd doctor of mine is faculty at the Mayo Clinic Medical College, is fairly extensively published and is a Fellow in Dr Cortes leukemia program (Scubas doctor, I think?) After seeing him, he referred me to a yet a 3rd Hematologist, also in Rochester, who specializes in transplants. This doctor was looped in in the event that I should need that transplant.

So I feel pretty solid about my team. I suspect their urgency with me is due to the clonal evolution. Hopefully when April comes around things will be promising enough to continue with Sprycel. (My primary Onc has already said he's strongly considering 20mg daily when I am able to resume.)

Scuba:

I can't tell you how helpful it has been to know about your story. It sounds like you've been in some of the remote corners that I've been bouncing around in recently. I don't assume any one thing will happen with me from here on out, but reading through many of your posts has at least given me cause for hope.

And indeed, after an inital blast count of 13% last September, by December they were just 1% (both via bone marrow aspirate). And that was weeks after my initial mere ~1 month of treatment at the time.

So I'm hopeful that blast trend holds after this recent treatment. I know you favor daily pills, but I was already stuck with the pills and every other day plan. I hope the next conversation will involve 20 mg daily. I agree... I think the myelosuppression might have forced me and my team to think differently about protocol. I am doing my part with your D3 advice (been taking 5000 IU + 90 mcg K2 daily for about a month). I'm also planning to add Curcumin to my daily regimen. It's ordered : ) So hopefully that helps me out. 

Thanks again, Kat and Scuba. Your kind and wise words mean more than I can say. I think many others here feel the same about you and others who take time out to encourage us newbies. 

This all sounds good, and April will be here before you know it.  I'm a little concerned that your second guy has mostly studied AML, which then (I would imagine, human nature being what it is) makes him hyper-concerned that he do everything in his power to keep you from ever having to face AML - in other words, he's too quick to intervene?  Worrying about and toward transplant?  A well-seasoned CML expert possibly would be more dogged and patient, balancing the TKI against the myelosuppression in a dance, as Scuba's story presents, and seeing how it plays out over a few months.  At any rate, good luck, keep reading and questioning, and keep us posted.

These guys.  They just don't realize how one word ("transplant") can turn our world upside down.  They're just musing out loud, considering all contingencies - you are the zillionth patient they've seen -  they totally forget that, to you, this is only happening to YOU.  Little anecdote here:  I was 27 with a brand-new baby and was told by a radiologist who scanned my thyroid, "Don't worry, there's a good cure rate for thyroid cancer."  Well.  In total panic and tears I called my primary care doc.  "Those radiology guys are ghouls!  Don't pay any attention."  All turned out benign.  I'll never forget the unnecessary suffering that one word cost me.  Nor will I ever forget how that kind doctor's single word ("ghouls" - isn't that great?) restored me.    

It’s true that when I saw my second doctor he said I am being treated for Accelerated (which confuses me because my blasts are 1%, when I thought blasts were the main marker for which phase you’re in), and that the next phase is called Blast Crisis, but it’s basically AML. And we don’t want to let me get to having AML. So that concern indeed is central to his plan for me. And in some ways BMT has an appeal. Right now it’s the only cure for CML, and they’ve already found multiple exact matches for me. However, my transplant specialist went into fine detail about the risks associated with BMT. I asked if anyone ever has a perfect outcome, he said about 30% do. Otherwise you’re looking at a 70% chance of varying degrees of GVHD, a relapse, or both. The 30% is obviously tantalizing, the 70% worries you. And if you fall into the 70%, is it the very bad end of that spectrum or more toward the management end of it. On balance I’m way more hoping for an effective low dose TKI approach, and then a minimal side effects, PCRU, and hopefully TFR scenario. And maybe a few years on they completely solve the puzzle. One thing I can absolutely say is that this forum has radically changed my perception of my situation, and for the better at least in terms of context.

I’m so sorry you had to endure that comment from the radiologist. You would really prefer that they just stick to their specialty and then stop talking. One time a radiologist was going on about how ‘long’ my lungs are. It can feel like you’re just a walking diagram to them. ‘Ghouls’... that was well played by your primary : )

Had my third biopsy and unfortunately blasts are now 69%. Eight weeks ago they were 1%. I’m floored.

I'm floored too.  I thought and hoped by now someone with expertise would have commented here.  I'm sure David/Alistair/Sandy will.  If you re-post over on the US LLS site, I am sure you would hear from Trey. 

There must be something else going on here.  More info is needed.  I am so sorry you are going through this!  Please hang on and don't give up trying - options (even including the transplant) are still available and you are going to come through.  Please keep posting!

Shortly after finding about the blasts I was given a unit each of platelets and blood. My numbers were so critically low (9 and 7.4 respectively). While doing that my Mayo Clinic hematologist called. He’s been working closely with my local hem-onc. Basically, he said he’ll see me early next week but he won’t know the plan until he gets the full report from my biopsy, plus some other tests I’ll do. I was then scheduled for a Tuesday appointment which includes another blood lab and an echocardiogram. He needs to know how strong my heart is to determine what options are available. That’s a little spooky. But without more information he couldn’t commit to any particular diagnosis or treatment plan, though he did say something about the possibility of giving me pills or keeping me there a “few weeks”. There was no mention of a transplant, which would be a three month stay, nor of the usual month treatment for acute. So that surprised me a little. But basically very little has been determined yet, other than my situation has taken a very sudden, very hard turn from last January. I do appreciate the words of encouragement.

I was diagnosed at, and use Mayo in Rochester. The great advantage is that the physicians work in teams and consult, so you never have to worry if one person is missing something. Their hospitals are excellent, great care and last year when I was hospitalized the food had become good. Hope today’s near blizzard misses Rochester Minnesota.  I wish you the best. Gitel

Bill, I'me very sorry to hear this, and I'm afraid your blast % is well outside my experience, and I think the experience of most of us. The further tests which you describe sound appropriate to find out what is going on. Please keep us informed. Fingers firmly crossed.

Thanks Gitel and Alastair. I am grateful for the kindness. I’ll try to share more information as I go through a tough stretch over these coming months.