Greg H - Vidaza as a Bridge to Transplant [Archive]

Greg H

Tue Apr 19, 2016, 03:42 PM

Hello All!

I've just finished up my first course of Vidaza, a drug that is supposed to reduce the number of immature white blood cells in my marrow and improve my blood counts as I move toward a stem cell transplant.

To recap, for those who haven't found my Campath (http://forums.marrowforums.org/showthread.php?t=1784) or Danazol (http://forums.marrowforums.org/showthread.php?t=2427) archives, I was diagnosed with low-risk MDS in March of 2010, with dysplasia in all cell lines, a duplication on the long arm of Chromosome 1, Trisomy 8, and HLA-15. All of that, combined with my relatively young age at diagnosis (53) made me a good candidate for immunosuppressants. I entered a trial of Campath at NIH in November 2010, but failed to respond.

A year later, I entered the Danazol trial at NIH, because they found a mutation in my TERT gene and extremely short telomeres. The Danazol worked well for a few years. But, after a (possibly unrelated) bout of acute necrotic pancreatitis and some heavy duty prednisone therapy, my need for bi-weekly RBC transfusions returned. A new biopsy found 15 percent blasts and progression to acute myeloid leukemia, landing me with an RAEB-2, high-risk diagnosis.

The folks at NIH and my local hematologist agreed that the only reasonable course of action was to ditch the Danazol in favor of Vidaza and to see a transplant specialist real quick.

As I mentioned at the outset, I have finished up my first round of seven Vidaza injections, given Monday-Friday of one week and Monday and Tuesday of the next. That is repeated in 21 days.

So far, the Vidaza has not killed me.

Important Note on Medical Terminology: When doctors say a drug is "well-tolerated" that means it is "unlikely to kill you outright." That does not mean it will all be milk and cookies.

Actually, the Vidaza has not been all that bad. It is not a harsh cyto-toxic (cell-killing) chemotherapy. So my hair is not falling out. It did, in fact produce three days of diarrhea (some folks evidently have constipation instead) which led to some dehydration, possible electrolyte depletion, and one day (#7) when I couldn't get out of bed until 3:30pm. On that day, it also produced notable brain fog.

The Vidaza IV is, in my cancer center, preceded by a dose of Zofran, to fight nausea, and dexamethasone, a steroid which is also used to combat possible Vidaza side effects. Based on my experience with Predisone while recovering from a nasty batch of pyoderma gangrenosum, I know I am sensitive to steroids. I have experienced some mania, euphoria, and emotionalism, as well as increased near-sightedness, since starting the dexa. And I also have significantly increased appetite. I have little doubt that I will also experience a considerable let-down once it is stopped.

It is quite possible that the Vidaza side effects -- particularly in terms of decreased blood counts -- will actually get worse over the next couple of weeks, as the drug goes to work on my marrow.

I do not currently understand how Vidaza works. I plan to find out and share it with you when I understand it.

I have an appointment with Dr. Mitchell Horwitz at DukeHealth on Thursday to discuss transplant. I hope that appointment will help define the timeframe of my future. I have a business to unwind, financial plans to make, family support to organize, and a host of other little details to work out.

PaulS

Tue Apr 19, 2016, 04:23 PM

Hi Greg - I've followed your posts over the years and thank you for sharing your experiences. I'm curious why you went down the clinical trial path instead of moving more quickly to transplant?

As far as Vidaza goes - I did one cycle without much success - then moved to transplant - the only drug they gave me was for nausea - I hadn't heard of giving steroids as a pretreatment - but I didn't have any noticeable side effects. Some have done very well with Vidaza - but it can take a while.

Do you have a match yet for your transplant?

Hope you do well going forward - a lot of people are rooting for you.

Best wishes,
Paul

Sally C

Tue Apr 19, 2016, 06:02 PM

Greg H

Tue Apr 19, 2016, 06:08 PM

HI Paul!

Thanks for your kind words. And excellent question!

Many folks -- including Dr. Danielle Townsley at NIH -- believe there is a "sweet spot" for MDS transplant, not too early and not too late. That sweet spot is when the disease begins to move from low risk to high risk and head toward AML.

Some of the pioneering work on this idea was done by Dr. Cory Cutler fifteen or so years ago. His research found that the best overall survival was obtained by transplanting at progression. Transplant related mortality is too great a risk for low-risk patients, who can survive for years with supportive care and other interventions like immunosuppression and Danazol. But transplanting is more risky once the patient has moved into AML. So you have to try to hit the sweet spot. There's a good respective and updates in a Cutler article here (http://asheducationbook.hematologylibrary.org/content/2014/1/77.full).

Townsley actually used the term "sweet spot" when she delivered her advice on my situation.

When I was first disgnosed, my local hematologist immediately set me up with an appointment for a port placement so Vidaza could be started, as well as a transplant consult. I visited with the transplant doc several times. And I started my own research. I found that transplant is risky and disruptive, the risk of relapse is high within five years, and that many folks, in addition to Cutler, felt it is not wise to transplant low risk MDS patients.

I found about immunosuppression and the Camapth trial at NIH. Talking with the principal investigator on that trial, Dr. Matthew Olnes, I found him strongly opposed to transplant for low risk, younger patients.

NIH is the pioneer in immunosuppression, and the Campath protocol seemed to hold more promise than ATG or Cyclosporine. So I went down that road.

As a result, I have had six years of remarkably good health -- which is likely more than I could expected from transplant.

But, as Dr. Townsley made clear, now is the time, and there is no reasonable alternative.

Thanks for your well wishes!

Greg

bailie

Tue Apr 19, 2016, 06:38 PM

Greg, again very interesting. I am in the middle of my 20th (and last) cycle of Vidaza (eight cycles pre-transplant and twelve after relapse after transplant). Remember that Vidaza often takes up to six cycles to be effective.

My interest in the telomeres was heightened when I relapsed. I had a lung fungal infection at about Day +210. Immediately preceding that I was on 160 mg/day prednisone and had the corresponding temporary Diabetes II. My theory (probably wrong, but I like it) is that this situation greatly shortened my telomeres and caused my relapse. Up until that time I was 100 percent donor cells. My relapse was strange in that none of the genetic mutations prior to transplant have appeared. Instead, I relapsed to AML and the "Philadelphia chromosome" which is a translocation of the 9th and 22nd chromosome (very rare). After three rounds of Vidaza and Sprycel (a TKI targeting the 9;22) I have been mutation free and doing very well physically. I feel fortunate in that I have had very little GVHD and feeling fine.
We will follow your progress with interest and hope you do very well.

PaulS

Tue Apr 19, 2016, 07:04 PM

Thanks for the interesting response - I was also advised with low risk MDS to wait - and did so until I was needing frequent transfusions, had excess blasts showing up (maybe 8% but probably lower) and a mutation (I don't recall what) that showed up briefly but disappeared before transplant. I tried EPO and Vidaza along the way, unfortunately without success.

My experience with watching and waiting was a slow but steady decline, waiting to get bad enough for transplant - exercising got harder with no hope of long term improvement - I found it fairly depressing - The positive thing about transplant is that it brought hope for being cured - and the prospect of continuously getting better and returning to normal activities - I felt a little more in control - I could maintain a positive attitude, force myself to move and eat - Although with plenty of bumps in the road - overall the experience has been inspiring.

I'm glad you've done well up until now - and am expecting you to fly through the transplant -

Best wishes

Paul

Greg H

Tue Apr 19, 2016, 11:57 PM

Hi Greg,
You may remember me - I too have followed you over the years as my husband is a fellow NIH patient.
I am so sorry for this turn of events. Please know I so wish you well. You are a brave soul with a wonderful wit that I know will help you in the coming weeks and months.
From one North Carolinian to another -
God Bless and best wishes,
Sally
Hi Sally!

Thanks so much! I hope you all continue to do well based on the eltrombopag.

This is a big adventure not necessarily of my own choosing, but the course of my disease makes it a pretty much inevitable step.

Thanks!

Greg

Greg H

Wed Apr 20, 2016, 12:03 AM

My theory (probably wrong, but I like it) is that this situation greatly shortened my telomeres and caused my relapse. Up until that time I was 100 percent donor cells. My relapse was strange in that none of the genetic mutations prior to transplant have appeared. Instead, I relapsed to AML and the "Philadelphia chromosome" which is a translocation of the 9th and 22nd chromosome (very rare).

Hi Baille!

Very interesting about the Prednisone. With my pancreatitis, I was prescribed 60mg per data first. But the hospital staff inadvertently gave me 120 mg in about twelve hours. That prompted a psychotic break with vibrant hallucinations lasting over at least a two day period. They eventually brought me down with haldol, I am told. It was a wild ride for someone who never dropped acid, I can tell you. This leads me to suspect that I am pretty susceptible to Prednisone.

When I left the hospital on 50mg per day, my HGB suddenly rose into the 12s for a few weeks, but then dropped precipitously once the taper began.

It all does lead me to suspect the prednisone as contributing to the worsening of my disease, but I doubt there is a way to establish that. And it did close up the hole in my belly, for which I am grateful.

Thanks!

Greg

PaulS

Wed Apr 20, 2016, 09:07 AM

Very interesting about prednisone - When I was diagnosed I was prescribed prednisone to treat painful skin nodules I would get - and had been getting for several years - the prednisone cleared them up with a high dose and we eventually settled on 10 mg per day which I was on up until the transplant. The prednisone did not cause a rise in HgB. This was a bit surprising since the skin nodules suggested an autoimmune component to my MDS.

We discussed the possibility of immuno-suppressant treatment for the MDS but felt that since the prednisone did not induce any changes in blood counts - that other immune suppression would also not work -

Greg - had you been treated with Campath yet when you were given the prednisone?

Hopeful

Wed Apr 20, 2016, 12:03 PM

Important Note on Medical Terminology: When doctors say a drug is "well-tolerated" that means it is "unlikely to kill you outright." That does not mean it will all be milk and cookies.

Ha Ha! I actually never thought about it that way, but it makes sense!

Like everyone else here, I am very sorry to read that your disease has come back and wish you continued strength in your fight.

I thought that it was interesting that you blamed prednisone for your current situation. When I first was diagnosed with very low but stable blood counts, my doctor tried 2 weeks of 100mg/day prednisone to see if that had any affect. My health and counts tanked during the trial and so I also think that it was a factor in my disease progression. My theory (and I always have one) :) is that in immune mediated bone marrow failure, the rogue T-cells are going crazy attacking the body's cells. Prednisone lowers the bodies immune system, but doesn't kill off the rogue T-cells. So whatever fight the body had left against the those bad cells, it loses. Just a theory...

I also have pancreas issues. Are you doing Pancreatic Enzyme Replacement Therapy?

Greg H

Wed Apr 20, 2016, 01:19 PM

Greg - had you been treated with Campath yet when you were given the prednisone?

Hi Paul,

Yes sir. I had Campath in November 2010, but didn't have any experience with Prednisone until November 2015.

Thanks!

Greg

Greg H

Wed Apr 20, 2016, 01:22 PM

I also have pancreas issues. Are you doing Pancreatic Enzyme Replacement Therapy?

Hi Hopeful!
I like your prednisone theory. I think the marrow is generally a very sensitive organ -- particularly among those of use who have some level of marrow failure. I recall that I had to stop exjade at one point because it was messing with my marrow.

I only have about on-third of my pancreas left, but, so far, I have needed neither insulin or replacement enzymes. I hope that holds up. It looks like transplant alone will have me on plenty of drugs all by itself!

Thanks!

Greg

Greg H

Sat Apr 23, 2016, 09:15 PM

Marcy and I journeyed up to DukeHealth in Durham on Thursday, for my initial transplant consult with Dr. Mitchell Horwitz.

I was really impressed with Dr. Horwitz as a thoughtful, careful, studious practitioner of the art. He took plenty of time, asked lots of questions, and cheerfully fielded lots of questions from us.

The initial objective was to determine whether I am a good candidate for a bone marrow transplant. The answer is Yes. Aside from my recent pancreatitis episode, I am healthy, without comorbidities like heart disease and diabetes. And I gave up all my debilitating vices years ago.

We plan to begin the donor search immediately, with the expectation that it will take 6-8 weeks. Meanwhile, I will continue my monthly cycles of Vidaza in an attempt to drive down the blast count in my marrow. The expectation is that we will move to transplant in about ten weeks or so -- that is, around the end of June or beginning of July.

The transplant-related question that remains is the type of conditioning.

Transplant typically follows one of two paths: fully myeloablative conditioning, in which we will attempt to totally eliminate my blood production system and replace it with a new one; or reduced intensity conditioning, using drugs that are somewhat less toxic and counting on the emerging new immune system from my donor to mop up the remnants of my blood factory.

Dr. Horwitz is inclined to go with a fully myeloablative conditioning. He explained that this is more likely to be curative and to avoid relapse after transplant.

However, he indicated that he wants to do some additional research to make sure that my TERT mutation and short telomeres do not mitigate against the high-intensity conditioning.

Which option we settle on will determine how long I am in the hospital -- as opposed to being treated on an outpatient basis. The fully myeloablative conditioning is also riskier up front because the drugs involved are more toxic and the process leaves the patient with no shred of a functioning immune system.

Neil Cuadra

Sun Apr 24, 2016, 01:41 PM

Greg,

Did it take Dr. Horwitz long to figure out what a well-informed patient you are? I hope he found it to be a pleasure.

The transplant-related question that remains is the type of conditioning.
You're in excellent hands to make this decision. Dr. Horwitz is one of the MDS specialists doing research on exactly this question. See:
Results of a Phase III Randomized, Multi-Center Study of Allogeneic Stem Cell Transplantation after High Versus Reduced Intensity Conditioning in Patients with Myelodysplastic Syndrome (MDS) (https://scholars.duke.edu/display/pub1123404)

Keep us posted on the donor search. Those of us who have had transplant experiences can share what we know, if it will help you with your own.

Greg H

Sun Apr 24, 2016, 02:50 PM

Thanks Neil!

I do try to do my research. I think Dr. Horwitz was a little surprised when I asked about a current trial he has going that involves injections of T-Cell Depleted Donor Lymphocytes as a way of minimizing GVHD. But it's a fascinating idea, and it's on Duke's webpage for him. That trial is just about full, evidently.

He has another one going that involves giving transplantees a drug that suppresses the secretion of pancreatic enzymes, the idea being that the harsh enzymes might be a cause of gut GVHD, just as UV exposure can be a trigger for GVHD.

Dr. Horwitz indicated that he'd be talking with me about clinical trials, and I'm all for that!

Take care!

Greg

Greg H

Mon May 16, 2016, 07:40 PM

Today, I sit on pins and needles in my very tiny hospital bed at Duke University Hospital.

[There are really, really smart people here, so it’s surprising to me that, when naming the place, no one figured out that “Duke University Hospital" was going to be abbreviated as “DUH”on every wheelchair, bed, and other piece of equipment. But the Duke Blue Devils were my Dad’s most favorite basketball team, and basketball was almost like religion for him, so I going to cut these folks some slack.]

I’m on pins & needles because my two high-powered docs are meeting to decide whether I continue with Vidaza leading to transplant, or if we charge on in with some induction chemotherapy and scorch the earth, figuring we get to transplant once that is done.

I wound up here because of a fever, of course. I spent four days in Stanly Regional Medical Center — my home hospital — with fever in late April, getting out just in time to attend the big MerleFest traditional music festival in North Wilkesboro, NC, where my daughter was performing and my Mom and Aunt Princess were attending.

I had a couple of fevers at the festival, and a lot of night sweats, but persevered until I returned home and, on May 4, had a sudden fever that spiked at 104.5 F. I was delirious, and my local hematologist sent me off to CMC Northeast, a hospital in Concord NC that has an infectious disease team. The idea was to see if they could discover the reason for my fevers and recommend some antibiotics.

After four days there, the blast count (immature white cells) in my bloodstream spiked up to 16%. That led to a concern that I had progressed to Acute Myeloid Leukemia [AML]. They shipped me off to Duke, since I’d already had a transplant consult here.

Now, on Monday, May 16, I am 12 days in hospital. Never forget, it is really hard to get out of the hospital, once you are in here.

My Docs — DeCastro and Horwitz — both brilliant, skillful, thoughtful practitioners of the craft, are to meet today to debate, discuss, and formulate a treatment plan.

So, I sit on pins and needles.

bailie

Mon May 16, 2016, 07:51 PM

Thank you for your information. I have coined a phrase, "susceptibility crisis" for my situations and maybe others. It is fitting in that my blast count increased and relapse occurred when I had my lung infection/surgery, prednisone and the associated short term diabetes. I have wondered how quickly telomeres can lose their length and make people more vulnerable during a "susceptibility crisis"?

DanL

Mon May 16, 2016, 08:06 PM

Greg,

I totally understand the whole once you are in the hospital thing. I spent about 80 days in and out of the hospital last year, some for pain management for my hips, then developed severe pneumonia, then had an infection in my line that resulted in the line being pulled. I was also in for recurrent cellulitis and swelling in my feet......totally awesome stuff, but 5-16 days per visit.

That being said I went into transplant with about 15% peripheral blasts, they may have dropped back down to 11 or 12%, but either way, they were high. I did a fully myeloablative chemo regimen though.

My guess would be that you would be doing a reduced intensity conditioning - maybe follow with some vidaza to help it along. I think that mausmish did this for 12 months afterwards because of her risk status. I took 6 months of vidaza after i relapsed 6 months after transplant.

I am wondering if you might want a little bit of gvhd to get a little bit of the graft versus mds effect. I know that gvhd can be a bit of a pain, but I am pretty sure that it has been responsible for continuing to fight off the disease. GVHD is definitely one of the morbidities to look out for, but relapse is usually really bad.

I did read an interesting article about controlling gut gvhd with basically butter extract - it looks like there is a compound in butter that protects the gut from GVHD - at least in mice - so if your cholesterol can handle it, extra butter on everything!

Good luck with the next few weeks and months as you begin making the big decisions again.

Dan

Sally C

Mon May 16, 2016, 08:23 PM

Greg,
Know that we are pulling for you. I so wish you well.
God Bless,
Sally

dsellers55@gmail.com

Tue May 17, 2016, 10:44 AM

Greg H

Thu May 19, 2016, 09:06 PM

On Tuesday, I had a phone call from Dr. Horwitz explaining why it makes more sense to begin induction chemotherapy — as though we were treating Acute Myeloid Leukemia [AML] rather than high-risk MDS -- as opposed to trying to continue on Vidaza.

He explained that he and Dr. DeCastro believe that all these fevers I have been having (every afternoon for the past four days), are not the result of some infection, but the result of the disease itself. Ditto the migraines, the knee pain, and the episode of stabbing pain in my eye.

My counts are terribly low. My white blood cells are three tenths of a point from zero. My platelets are trending down every day, approaching 10, where you have to have a transfusion or risk bleeding out. These are the kinds of counts you get with the conditioning chemo for a transplant. And they make it unlikely that I could return home to resume Vidaza over at Levine Cancer Center in Albemarle.

So, we are going to Plan B, which we had discussed in our initial visit with Dr. Horwitz. I had a two lumen Hickman catheter implanted in my chest yesterday and last night at about 10 pm we began the first day of seven days of serious chemotherapy using cytotoxic drugs.

I’ll have seven days of continuous Cytarabine. The first three days I will also have Idarubicin.

These will make my hair fall out, though my beard may not.

The drugs will suppress all my counts. The idea is to clean out the bad stuff in my marrow, and have the remnant regrow a new blood production system.

After the therapy, Marcy and I will need to stay 3-4 more weeks in the hospital, waiting for that regrowth. After that, we may be able to stay at home for a week or so, until they are ready to do the transplant.

Normally, in AML therapy, after a few weeks, you have another smaller dose of 2-4 chemo drugs. It’s called consolidation. But, in this case, we will move transplant instead. The goal there, of course, will be to transplant my existing blood production system — which we know is kind of junk, because of the TERT mutation and short telomeres — with a new one.

So, this will mean a longer stay in Durham for Marcy and me.

But it seems like the most reasonable course of action given my counts.

Dr. Horwitz and I have not discussed the transplant regimen, which I reckon will be highly dependent on how well I have responded to the induction chemotherapy.

So, it's needles. And I am good with that.

Greg H

Thu May 19, 2016, 09:11 PM

Hi Greg, just reading about what all is going on. Thought I would let you know it all seems very complex and you are very well educated on your disease. Please know you are lifted up each day!
Blessings,
Tim

Thanks, Tim!

And the same to you. Glad to see you on here; folks here have been a big help to me.

When I was first diagnosed, six years ago, I read everything credible thing I could find about disease. That put me on the clinical trial path, 'til disease progression knocked me off that horse in April.

It's funny, one thing I don't know much about is myelofibrosis. But my last BMB says I have it now, so I am going to have to do some reading.

Take care of yourself, friend!

Greg

Greg H

Thu May 19, 2016, 09:12 PM

Greg,
Know that we are pulling for you. I so wish you well.
God Bless,
Sally

Thanks, Sally! You're the best!

I am really confident in these Duke folks.

Greg

Greg H

Thu May 19, 2016, 09:26 PM

My guess would be that you would be doing a reduced intensity conditioning - maybe follow with some vidaza to help it along. I think that mausmish did this for 12 months afterwards because of her risk status. I took 6 months of vidaza after i relapsed 6 months after transplant.

I am wondering if you might want a little bit of gvhd to get a little bit of the graft versus mds effect. I know that gvhd can be a bit of a pain, but I am pretty sure that it has been responsible for continuing to fight off the disease. GVHD is definitely one of the morbidities to look out for, but relapse is usually really bad.

Dan

Dan,

As usual, your extensive research has allowed you to deduce exactly the struggle that I see going on in Dr. Horwitz's mind. My TERT mutation and short telomeres have him worried that I might have a more fragile than usual marrow, which make him lean toward reduced intensity conditioning.

On the other hand, he knows, and his former NIH colleagues are reminding him that a fully myeloablative conditioning regimen is a better guarantee of relapse-free survival.

That's why I think he will wait to see how the induction chemo goes, before making a decision.

One thing I haven't discussed with either Horwitz or NIH is whether, once we are done with induction, and waiting for my blood system to rebuild, we should add Danazol to the list of meds.

We know I have the mutation and short telomeres. We know I respond to Danazol. So, why not try to help the recovery process along with a little Danazol boost?

The counter arguments I see are that no one has ever done it and that Danazol seems to take months rather than weeks to work its magic.

Still, I am going to bring it up.

Take care!

Greg

PaulS

Thu May 19, 2016, 11:17 PM

Hi Greg - I also had Myelofibrosis - My doctor thinks it contributed to the relatively long time it took my counts to rise post transplant - it was harder for the new stem cells to find a home due to the scarring - he said it would take a year or so to go away post transplant - although the last BMB didn't show any - but he thought that was due to the BMB sample and not necessarily the Myelobirosis away - I'm, however, going with it went away - got a BMB next month, so we'll see.

I'm not sure I understand the reduced conditioning BMT - I received non-myeloablative conditioning due to co-morbidities - otherwise I would have had myeloablative conditioning with t-cell depletion - but transplant centers and doctors all seem to have their preferences - but it is interesting how many different approaches there are to similar problems - its all a bit of an art I think.

Glad you seem to be maintaining a positive attitude - I think that's very important.

Hope the food is good in the hospital -

Best,
Paul

DanL

Fri May 20, 2016, 03:12 AM

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

Sun May 22, 2016, 04:47 PM

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

Sun May 22, 2016, 06:41 PM

Cheryl C

Mon May 23, 2016, 07:11 AM

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

Mon May 23, 2016, 10:19 AM

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

Mon May 23, 2016, 08:58 PM

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

Wed May 25, 2016, 08:34 AM

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

Wed May 25, 2016, 08:50 AM

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

Wed May 25, 2016, 09:30 AM

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

Wed May 25, 2016, 09:35 AM

"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

Wed May 25, 2016, 05:03 PM

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

Thu May 26, 2016, 07:41 AM

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

Fri May 27, 2016, 07:47 PM

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

Sat May 28, 2016, 11:46 AM

Greg H

Sat May 28, 2016, 02:40 PM

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

Sun Jun 19, 2016, 07:12 PM

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

Mon Jun 20, 2016, 08:24 AM

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

Sun Jun 26, 2016, 01:29 PM

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

Sun Jun 26, 2016, 01:33 PM

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

Mon Jun 27, 2016, 03:08 AM

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

Mon Jun 27, 2016, 09:58 AM

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

Mon Jun 27, 2016, 12:17 PM

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

Wed Jun 29, 2016, 12:50 AM

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

Shikha tomar

Thu Jun 30, 2016, 05:10 PM

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:cool:
Pentids
Bactrim
and now Revolade because of low platelet counts

DanL

Fri Jul 1, 2016, 02:41 AM

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