Greg H - Vidaza as a Bridge to Transplant

[DanL]

Greg,

As you know, I had grade 2 to 3 fibrosis in my marrow as well. Engraftment took a little longer - at 31 days, i was only at 500 ANC, but was producing RBC and platelets nicely. All fibrosis was gone within 3 months according to my biopsies.

It is an added factor, but the treatment is the same - transplant is the only cure possible. They do use a lot of danazol to help treat patients with myelofibrosis, so it seems like a logical addition, but it may also add the possibility of allowing gvhd to come after the lungs....just a thought.

I would also say that with full induction chemo, you are dong the equivalent of a fully myeloablative regimen, so a ric at transplant seems to make sense there rather than subjecting you to consecutive fully destructive regimens.

I have you in my thoughts and pray for the very best outcome for you. Stay positive and know that you will succeed.

Dan

[Cheryl C]

Greg - all the very best as you commence the transplant process. Your posts are always so informative and positive. Thank you.

Really interested in the comments about Prednisone. After many years with neutropenia my MDS was diagnosed a couple of months after I had been treated with Prednisone for bacterial bronchitis. That was when my blasts appeared.

[bailie]

Cheryl, it was Greg who made me a believer that it is short telomeres as a result of prednisone, diabetes, infection or similar events that create a susceptible situation for relapse or increase in blasts. The short telomeres will be the key that unlocks the mysteries of our diseases

[Cheryl C]

Yes, Bailie. Very interesting. What sort of test is done to determine whether one has short telomeres? (I'm being lazy here as I'm sure this has already been explained by Greg).

[bailie]

Greg is the person to answer that question. He has had his measured. I haven't had mine measured. I asked to get mine measured but it is not a standard practice yet.

[tytd]

Greg,
I am sorry to hear that you have relapsed and are having to go through induction therapy but believe you are in good hands at Duke. I learned a lot from your posts when I was haunting this website back several years ago and wanted to thank you for it. I am very thankful for the stability of my disease and the adversity certainly has taught me a lot. I did initially see a Dr. A at Duke in 2008. You might be interested in another patient's (Chris) blog posting his journey entitled "The Marrow Chronicle". He is apparently 3 years out from a transplant at Duke. He probably is in the archives of Marrowforums. I wish you a smooth and successful treatment course. Marie

[Greg H]

Originally Posted by tytd

Greg,
I learned a lot from your posts when I was haunting this website back several years ago and wanted to thank you for it. You might be interested in another patient's (Chris) blog posting his journey entitled "The Marrow Chronicle". Marie

Thanks, Marie!

I have learned so much from the folks on marrowforums that I set a a goal of trying to bring back to the community everything I have learned about the disease. I see this as a real communal effort to take hard-to understand medical lingo and get it down into plain language. My posts were less frequent for a while, once Danazol worked for me, because, as Dr. Bogdhan Dumitriu put it, I was not sick anymore.

But I am back with a new MDS adventure, and hope to be a more frequent contributor, assuming I can write through the side effects of chemo.

Thanks for the tip about the Cap's blog. Someone else clued me into that one and I read the whole thing. I was very sorry to hear that he wound up with GVHD issues three whole years after transplant but was glad to hear he had finally been able to play his guitar and fiddle.

Take Care!

Greg

[Greg H]

Originally Posted by Cheryl C

Yes, Bailie. Very interesting. What sort of test is done to determine whether one has short telomeres? (I'm being lazy here as I'm sure this has already been explained by Greg).

Hi Cheryl!

I used to know the answer to this question, but have forgotten. I'll go find out. As I recall, there are a couple or three different measurement techniques.

Thanks care!

Greg

[Greg H]

Originally Posted by bailie

Cheryl, it was Greg who made me a believer that it is short telomeres as a result of prednisone, diabetes, infection or similar events that create a susceptible situation for relapse or increase in blasts. The short telomeres will be the key that unlocks the mysteries of our diseases

Hi Bailie!

I think this is why telomeres are such a hot topic among the researchers. I've been told that my current principal physician, Dr. DeCastro, has been doing telomere work, though I haven't had a chance to speak with him about that yet — or look for any papers.

Take Care!

Greg

[Greg H]

"And it's no never in the livelong day,
Will you find me back in Durham Jail.
No never in the livelong day,
Will you find me back in Durham Jail."

That traditional English song seems a fitting marker for today, my twenty-eighth in hospital and my seventh, and final, day of a seven day course of induction chemotherapy.

Here is Jez Lowe's version of the song:

https://youtu.be/oor6H2BA5gQ

I have joked with the medical staff that I have seen most of the odd spots in this Durham hospital but have yet to locate the parole office.

My primary health complaints since entering the hospital have been:

- Fever, which landed me here in the first place and expressed itself every day or two, typically in the afternoon, presenting with chills and rigors and knocking a five-hour hole in the day.
- Headache. Daily, fierce migraines began on the day I entered the hospital.
- The yips. This is my own decorative name for a condition that arose a week or so ago, in which walking or standing, to Starbucks or in the shower, produces pressure on my knees, setting up some neurological cascade that runs up my legs and spine into me shoulders and leaves them pulsing for thirty minutes to an hour.

Fortunately, the first two of these have been resolved by the chemotherapy itself. The fevers disappeared after the second day of chemo. The migraines have also apparently departed. My first migraine-free day was the result of a dose of Toradol (keterolac) that I received for the yips four days ago. Toradol is an amazing NSAID, but limited to very short-term use, and hard on platelets, which I have precious few of to begin with. So the Toradol was not repeated. Nevertheless, I have gone the past two days without migraine.

The Yips remain a problem. I received Neurontin last night to see if that might help, so we shall see.

The docs and nurses tell me that, with wrapping up chemo, next week and the next will be the toughest part of the process, with unavoidable small infections — and the antibiotics they occasion — sapping energy.

Given that, I reckon it’s better for me to be here in Durham Jail than on the outside.

[bailie]

Greg, this is what got me out of the hospital after transplant. It worked and they started cutting orders right after I broke out in song.

https://www.youtube.com/watch?v=CAg1uf-Si2k

[Greg H]

Originally Posted by bailie

Greg, this is what got me out of the hospital after transplant. It worked and they started cutting orders right after I broke out in song.

https://www.youtube.com/watch?v=CAg1uf-Si2k

The guys at recreation therapy here have given me a guitar to beat on, so I may be able to effect the same escape strategy!

Greg

[Greg H]

It's day nine after the beginning of my induction chemotherapy at Duke University Hospital, and I am waiting for the other shoe to drop.

I do find myself a bit more fatigued each day, but that didn't stop me from walking a mile and a half in the halls both yesterday and today.

It does, on the other hand, lead to a kind of paranoia, with every little pain shooting through my head a sign of stroke and every gurgle of my stomach a sign that the dreaded gastrointestinal plague has arrived.

To give you an idea of how bad this gets, last night, I found myself experiencing pressure in my chest while sleeping. I have discovered that the secret to hospital life is to retire shortly after supper, because you are going to be awakened multiple times during the rest of the evening.

So, I am lying in bed, more than half asleep, with pressure in my chest, worrying about whether I should acquaint my nurse with this problem.

The odd thing about this pressure was that it had a distinctly rectangular aspect -- it felt like someone had squeezed my lungs into a box. It went on pretty much all night, with me drifting in and out of sleep.

I awoke this morning to the realization that I had gone to sleep with my iPhone in my hospital Johnny -- the source of the pressure and its distinctive rectangularity.

Both my nurse and the doctors leaned in when I mentioned the pressure -- and cracked up when I spilled the beans about the iPhone.

Still, it's a good example of what it feels like to be waiting for the other shoe to drop.

[bailie]

Greg, you are doing much better than I did. I was given Fludarabine for three days and then Melphalan on Day-1. The first two days I thought I was doing well walking five miles each day, then it hit me. The next day I could barely get out of bed. That continued until about Day+10. I slowly built my stamina after that. Keep it going!!

[Greg H]

Originally Posted by bailie

Greg, you are doing much better than I did. I was given Fludarabine for three days and then Melphalan on Day-1. The first two days I thought I was doing well walking five miles each day, then it hit me. The next day I could barely get out of bed. That continued until about Day+10. I slowly built my stamina after that. Keep it going!!

Bailie, I feel quickly to sleep right after finishing my lunch tray today. I think the fatigue is growing gradually each day for me. I'm sleeping a ton at night, but still needing an increasing long nap in the afternoon. If a lot of sleeping is as bad as it gets, I will be grateful.

Take Care!

Greg

[Greg H]

I wrote this post eight days ago and never managed to get it online. An update should be coming shortly.


That’s the essence of our time here at Duke. We are 25 days in from the first day of chemo, and we’re still waiting to see what it did, so we know what we need to do next.

My docs did a bone marrow biopsy on 5/31 - Day 14 - which is the standard course of treatment here. It took couple of days to get the results.

The BMB found that I still have five percent blasts (those pesky leukemia white blood cells), but my marrow is so hypocellular (or aplastic) that it’s not clear whether those blasts are new ones produced by cancerous stem cells (called “clones”) that were not killed by the chemo or if they are leftovers that will eventually be killed by the chemo, which my docs reminded me is still working. This I know to be the case because it is gradually subtracting hairs from my head and face.
*
Hypocellular marrow is not uncommon at this stage of induction chemo; mine is at 5-10 percent. A normal person of my age (60 in November) would have cellularity of about 40 percent. What we are waiting for now is for the marrow to rebuild itself after the chemo shock.

Because I had MDS before an explosion of blasts lifted my disease into higher-risk status, my marrow is expected to rebound more slowly. Think about it: MDS is a disease in which some of your bone marrow stem cells are defective and produce blood cells that don’t mature properly, or are broken in other ways. Kicking out the leukemic stem cells (which produce blasts) doesn’t fix these broken MDS stem cells.

So, as my marrow recovers, both MDS and non-MD,S stem cells will be part of that recovery. That means a percentage of my newly recovered cells will be junk. So, it could take a bit longer for my counts to increase.

Tomorrow is the beginning of the period when a response is expected; it’s probably more realistic to expect a response from my marrow a bit later in the month.

That’s the big picture. On the small picture side, I’m having trouble with pain in my knees, hips, and lower back; the occasional fierce headache; and fevers most every day. The fevers appear to be a result of the disease itself, rather than an infection. All but one of my blood cultures (of which I have had many) have come back negative. The exception grew a gram-postive Staph epidermis bug, which was wiped out the next day by Vancomycin.

I have a rash covering my entire abdomen that the docs explain is *reaction to medication. Fortunately, it neither burns nor itches.

So we wait. And transfuse. And imbibe lots and lots of antibiotics.

[lisa3112]

Hi Greg,
You sound like you are doing well and dealing with all this in such a positive way. Having a biopsy that early seems a bit rough! What difference would results make then I wonder. I actually had a biopsy today... day 91 post transplant. The waiting for results is the worst! I worry a bit because I have active cmv and my platlets dropped a bit... but could be from vangancyclovire or cmv itself. Anyway good luck with your counts... mine took 30 days or so to start moving at induction. Lisa :-)

[Greg H]

Originally Posted by lisa3112

What difference would results make then I wonder. I actually had a biopsy today... day 91 post transplant.

Hi Lisa!

I think the protocol they were more or less following with me was the one for AML patients who are not headed to transplant, because I didn't yet have a donor lined up.

Still, that seemed pretty early to me, and Dr. DeCastro has a nice paper arguing that a day 14 or 15 marrow doesn't make much sense. I know that folks at the big hospital down in Charlotte no longer use it, and I'll bet that's the case elsewhere.

Take care!

Greg

[Greg H]

You’ve been in the hospital too darned long. The hospital Johnny, for those of you who haven’t had the pleasure, is a dress-like garment that wraps around you, tying at the neck and roughly at the waist, famously leaving way too much of your skin or undergarments exposed.

Worse, it has snaps running up both sleeves. These allow easy access to, for example, the lumens of a Hickman catheter implanted in the chest. But it is maddeningly difficult to figure out how to snap those snaps in the proper order.

Well, after 53 days in hospital, I have it down cold — which means it is time to go.

Fortunately, my doctors think so, too.

I don’t have a copy of my most recent bone marrow biopsy pathology report, but I have the gist of it. My marrow is very scarred — very “fibrotic” — and the pathologist’s report from staining the marrow finds ten percent blasts, up from five percent last time. Again, that number needs to be taken with a bit of salt, because I have very few cells to speak of overall. Unfortunately, without the report in my hands, I can’t speak to exactly how hypo-cellular my marrow is.

In any case, based on those results, Dr. DeCastro and Dr. Horwitz put their heads together and decided the best course of action is to send me home for some R&R.

DeCastro sees that 53 days in the hospital has taken its toll on me, so he’s not ready to do more chemo.

Horwitz probably feels the same about transplanting someone with that much time in hospital, and may be skittish about transplanting someone with ten percent blasts.

So, if Horwitz is not going to transplant me, and DeCastro is not going to give me more chemo, what am I doing here?

There are really two key factors to getting me home:

Getting the nearly nightly fevers I have been having under control. DeCastro’s team has pretty well determined, through an abundance of blood cultures, chest X-rays, CT scans, and so on, that the fevers are caused by my disease, not by an infection. So, we need to stop them from happening, so that, if I am at home two hours away in Mt. Gilead, Marcy is not schlepping me to Durham every night with a fever. Tylenol alone didn’t make this happen, so they’ve added low dose prednisone.

Keeping the platelets above 10 for seven days. Under 10, platelets present a serious risk for a bleed. For instance, falling and hitting your head could cause a brain bleed. We are making real progress in this regard. I appear to be making platelets. I haven’t gotten to a seven day transfusion interval, but I have done six. Seems likely we’d want to do a mid-week check at the local cancer center anyway, just to be safe — so, six may be good enough.

All of this should be resolved this week, or the next. Keep your fingers crossed!

[DanL]

Greg,

Glad to see that you are out of the hospital. About the blasts - I was transplanted with about 12% blasts. The magic number seems to be about 13% - at least as far as relapse is concerned. You mentioned that they had not found a donor just yet. I am sure that you have looked into haploidentical transplants. The results out of Johns Hopkins have been pretty positive, but I am not sure what their patient selection bias was when doing their study, and I am not sure what your prior chemotherapy and treatment options does to eligibility.

Either way, I am very glad that you are out and home for a while anyway.

Dan

[tom30]

Hi Greg, I have my fingers crossed for you. I'm rooting for you, I know you will not give up. 53 days in the hospital is rough but I'm sure you are up for the challenge. You have been a inspiration to me personally I appreciate you sharing your experiences. I have been and will continue to pray for you to beat this.

[PaulS]

Hi Greg - I'm rooting for you too - your positive attitude has been an inspiration to me too - and I'm sure many others. Is a halplo/chord transplant an option for you? I was told the long term outcomes were about as good as a regular transplant - with less GVHD but longer time engrafting and more risk of short term complications. but I'm sure your on top of this and asking all the right questions.

Best wishes,
Paul S.

[Hopeful]

You are in my thoughts, Greg. I hope you are rejuvenated by your time at home. Be well!

[Shikha tomar]

My mothers mds relapsed and as dr. Suggested she had alloHsct 6/6 Match..on aug-2015
after transplant she recovered platelet but her hb was always around 6-7,,,now she has irritation in her eyes and sore throat + Thrombocytopenia (platelet count=29,000)
her biopsy report shows insufficient stem cells...shes on cyclosporin and many more drugs.
dr.'s have no idea whats the reason behind it but as i was going through so many articles i found one which says irritation in eyes is related to cgvhd and that thrombocytopenia thing is may be because of secondary failure of platelet recovery.
please anyone here who had similar problem
what kind of treatments are available for such problem. I want to know more about this SFPR thing.,
please somebody help!




----------------------------
MDS relapse allohsct performed on 18-aug-2015, 18% Blasts Had mild gvhd ,
+317day , low platelet count 29,000
lowTLC..irritation in eyes and sore throat! ( Mild cgvhd)
prescription
Acivir
Cyclosporin
Pentids
Bactrim
and now Revolade because of low platelet counts

[DanL]

Shikha,

Please forgive me if I misspelled your name, my eyesight is a little poor since my glasses are not near. Low platelets after transplant can be caused by a number of things, including graft failure and relapse - these are the worst case scenarios. The other two culprits are drug interactions and immune suppression. Looking at the list, Pentids and Bactrim could be causing platelet suppression as these are known side effects, so reduction in dose, or drug replacement may help - Many doctors use Pentamidine treatments to replace Bactrim, but Bactrim is more convenient and a little more reliable than Pentamidine, although Pentamidine is only once monthly inhaled at the hospital. I am not sure what would be the appropriate replacement for Pentids, but usually preventive antibiotics are pulled within the first year - so it may not be necessary to continue - talk to the doctor about this. Withdrawal of these medications or replacement could be appropriate. The other culprit of platelet suppression or destruction is immune suppression. There are a lot of different drugs that can be used. Cyclosporine is pretty common due to cost, but like all drugs affects different people in different ways. tacrolimus, sirolimus, mmf, and several others are potential alternatives. I am about 2.5 years post transplant and had low platelets - about 50k until about 1.5 years out from transplant. I was on a lot more immune suppression than i am on now.

If graft failure or a weak graft is suspected, then it is possible that a donor lymphocyte infusion might help, assuming that there is no additional disease hiding out.

A couple of other ideas for GVHD or weak graft could include things like vidaza or rituxin, but these are completely experimental with what you described and would require somebody with far more knowledge than i have to offer.

I hope this helps a little in your future conversations with the doctor. I think that you can bring up these items as questions to see how the doctor responds and see if they are able to give you a little more rationale as to the current approach and see where treatment should go.

Has your mother had a recent bone marrow biopsy and aspiration? Has she had her chimerism checked? Do you know her marrow cellularity at this time?

Dan