Inspirational thoughts about "New Beginnings"

There are two mistakes one can make along the road to truth..not going all the way, and not starting

-Hindu Prince Gautama Siddharta, the founder of Buddhism, 563-483 B.C.

Wednesday, January 26, 2011

Negative, Negative, Negative, Negative

That's one for each month since no TKI!!!!

Sorry it has been awhile since I last updated this blog but things have been incredibly busy. When we last met here, I was getting ready for the November check up and PCR draw. My how time flies!

I am very happy to tell you that November, December and January PCR's are all NEGATIVE!!!!

There is something else quite interesting happening. As you may recall, although I stopped the low dose of Sprycel, I have continued on a very small dose of Peg IFN. The dose was 90 UG once a week. Notice how I am using the past tense? This dose usually did not represent any side effects for me, and I found it very easy to tolerate it. But that changed in early December. It seems that the combination of a TKI and Peg IFN may have, at least in my case, re-sensitized me to IFN. So we negotiated a decrease in the dose to 45 UG once a week. I have to be thoroughly honest with you, during the holidays the side effects of the Peg IFN had gotten so bad, which never, NEVER happened to me before, that I actually gave myself a holiday for just over two weeks - no drugs, yet the PCR is still negative....That is very significant for me.

There is much more going on, but I cannot share all the details just yet. I can give you a hint, we are looking at my immune profile and a variety of other things. We are also investigating the possibility that the Peg IFN may have caused some sort of arthritis, but I am not worried about that so much, as the joint pain goes almost completely away when the drug is stopped. This makes me think that this is a drug related problem that may be easy enough to resolve, just stop the IFN, which I want to do, but which we are waiting until we establish a trend...Remember wean off the TKI, then wean off the Peg IFN, then cross our fingers and continue to closely monitor the situation....

I am not going to lie to you, this is scary sometimes. Especially with the joint pain, I can convince myself, late at night of course, that the CML is back. But the PCR and my blood counts all show that it is not.

My next appointment is in a few weeks, but I am savoring this moment for now and relishing in the idea that I just might have beat this thing. Why not think positive? It is so easy to think negatively. For now the only thing negative I want in my life is negative PCR values.....

Just recently we celebrated the 50th anniversary of President Kennedy's inauguration. He followed his words with actions. He dared Americans to think big and reach for the moon even though we barely had any tools to dream such big things...

His Brother Robert Francis Kennedy quoted George Bernard Shaw, "You see things; and you say, 'Why?' But I dream things that never were; and I say, 'Why not?' (from the Plays Back to Methuselah: In the Beginning, Bernard Shaw: Complete Plays and Prefaces, Vol. II, page 6. (Dodd, Mead & Co. New York 1963)

This is what we all must continue to think about - the "Why Not?" JFK showed us that the only thing stopping us from moving forward was ourselves. If we could just get over ourselves and work together, we could reach the moon. Another great President, FDR at his first inaugural speech said "The only thing we have to fear is fear itself". Just recently President Obama told us " We Do Big Things"....Each of these presidents were in office during very difficult times for America, not so much unlike a diagnosis of cancer....They led by example and we all persevered...

Great things are happening. At the very least this experience will teach us something or add another piece to the puzzle for us.

In the distance I hear the sound of somebody opening up a can of "Whoop ASS". Watch out quiescent CML stem cells & minimal residual disease, many of the top CML researchers and doctors in Europe, America and Australasia are on the move, and "we gonna find you"....

Wednesday, November 17, 2010


One PCR result does not a trend make - but I'll take it for now and revel and celebrate just the same!

For one thing, the last time I stopped a TKI and switched to monotherapy IFN, within two weeks I was no longer PCRU, I was MMR, and then in another two weeks after that I was at CCR, but I stayed steady at CCR - until switching back to a TKI AND IFN...

I am pretty sure you might have guessed by now that the result from the October draw, taken one month after stopping TKI is - drum roll please.... NEGATIVE....

My next check up is this coming monday, and we do another draw which will tell the tale of two months of no TKI therapy. You might be wondering how do I feel? Well I feel very good actually, less fatigued, less achy. But it is more than just those physical things, there is a deep feeling of wellness that I cannot even begin to describe. It is something that I believe I haven't felt in, well, decades...

What's even more interesting is that people are commenting that I look different. I am not sure I look different as much as I feel different, but maybe it might be because I am just smiling more?

The period of time spent waiting for the results of the PCR draw was a time of good reflection for me. It occurs to me that CML in most cases, creeps up on us so slowly and insidiously that when we think about it, we cannot remember the last time we felt perfectly well. A few weeks ago I was meditating on my childhood and I was especially thinking about my "active" childhood. I remembered summer vacations with the family on Cape Cod, the smell of the salty air. The crispness in the very early morning and waking up really, really early, full of energy. If the tide was low, we would run down to the beach and go clam digging or wade out a bit and go quahogging. Then we would set off on other adventures, like rowing the Sinbad around in the bay, riding our bikes for miles or walking to the golf course at dusk with our hoodies on to watch the bats collect on the water tower....Back in New York, I was just as active - running, riding my bike or swimming forever...It was very good to take this reflective journey through meditation back to my childhood. It gave me time to think about how much I missed that energy. Happily some of it is coming back. When I work out in the mornings I push myself a bit further, sometimes my lungs burn just a bit, but it is a good burn, the kind of burning feeling when we were young...The good news is that I seem to recover much faster, and sleep a bit sounder....

There is no way to know how long this will last. According to the literature, I probably still have the original LSC. But I am not going to ponder on that for now.

What I am most grateful for at this moment is the fact that I feel well, I am happy, and that I am experiencing some downtime from drugs and CML.

In my excitement to spread the good news it became painfully evident to me that in my entire network of fellow CMLers - which is very extensive, I know of only three people who can entirely relate to what is going on for me at this time.

So, my meditative thought for today and for the next while is that there needs to be more opportunities for my fellow CMLers to get on this very path and be able to experience a safe break from drugs.

May we all be well and healthy!

Thursday, October 21, 2010

The Greatest Discovery....

A splash of some tap water onto a few slides containing the blood smears of patients diagnosed with CML led to an interesting and significant discovery.  It was 1960 and the study of the human chromosome was in its infancy.  Well, actually, it was more like it was a neonate, after all it had only been determined just two years earlier, in 1958, that humans had 46 chromosomes.  This was why, when Peter Nowell looked at his slides after inadvertently splashing them with tap water, he wasn't really sure what he was looking at.  What he was looking at was chromosomes.  It seems that tap water on slides caused the cells to expand, spilling their chromosomes.  Lucky for all of us it just happened that he had slides of cells that were dividing.   Another piece of luck came when Dr. Nowell decided not to throw the slides in the rubbish and brought them to someone else to have a look.  This led him to collaborate with Dr. Hungerford and together these two scientists discovered the abnormal chromosome in patients diagnosed with CML, which we know as the Philadelphia chromosome.  This was a great discovery, because now that we had this piece of information we perhaps could find out what caused it.  Enter Dr. Janet Rowley, MD.  Dr. Rowley had the foresight to preserve slides of specimens from tissue and blood smears taken from her CML patients.  In 1973 a new technique was perfected that allowed human chromosomes to be banded.  Banding means that we can see the various sections (genes) on each of the chromosomes.  Using this technique we can Band our chromosomes which is called karyotyping.  That means we can see each of our chromosomes and its various sections.  Human cells have 23 pairs of large linear nuclear chromosomes, which is actually 22 pairs of autosomes and one pair of sex chromosomes.
Dr. Rowley decided to use this new banding technique to karyotype the specimens she had saved from her CML patients.  Sitting at her dinning room table, she was after all also a working mother and wife, she saw a pattern emerge and realized that the odd chromosome, the Philadelphia chromosome, was actually a translocation.  A translocation is when some genetic material from one chromosome exchanged some of it's material with another chromosome.  She felt that this translocation caused cancer.  
By 1983 we would have the proof, thanks mostly to the work and efforts of a team led by  Nora C. Heisterkamp, PhD.  She had localized c-abl adjacent to a translocation break point named BCR – which stand for breakpoint cluster region (which describes what it does). So, now we had a target c-abl and BCR, or as we know it today, BCR ABL.  

Owen Witte determined that BCR ABL fused causing a fused protein that was a tyrosine kinase.  The Tyrosine Kinase is a protein that can control other enzymes, and in the case of CML it leads to deregulated cell growth, meaning cells do not die, and they grow out of control.  Work done in a lab by Dr. Levistki showed that Tryphosptins could inhibit tyrosine kinases and Jurg Zimmerman and Nick Lydon from (Ciba Geigy which had merged with the company called Sandoz) Novartis had a molecule in their lab that was being tested for glioblastoma's.  With just a bit of tweaking of this molecule a new compound was formed and was finally tested in humans in 1998.
The results were astounding!  Gleevec is a molecularly targeted therapy that is very effective in stopping the erroneous signal and targets only the cancerous cells, leaving healthy cells alone.  Patients given the drug did remarkably well in the first clinical trials, and they continue to do well even today. 
However, as Dr. Sawyers tells us, even during the phase I clinical trials there was evidence of drug resistance.  Lucky for us that Bristol Myers Squibb had a molecule in their lab that worked well against various mutations that can develop when the disease does not respond to the drugs.  But, I do not want to get ahead of myself....
Now that Novartis had a drug that worked, they were faced with a very significant challenge.  How do they bring the drug to market when there are so few patients?  They designed a very strategic business plan pricing the standard dose of Gleevec (400 mg daily) roughly equivalent with the front line therapy of the day, 10 million units of interferon.  When it was launched Gleevec cost about $3,500.00 for a thirty day supply of 400 mg daily.  
The good news was that patients were doing very well and saw a dramatic improvement in their quality of life as well as very good control of the disease.  However, it was still very difficult for patients to access the drug.  Novartis did a very good job of establishing patient access programs.  The cost of the drug not only covered the cost of the research and the massive investment Novartis made to bring the drug to market, it helped to support programs that made the drug accessible to more patients.

We have often been told that Gleevec doesn't cure CML, yet in 2005 we started to see signs from Europe that perhaps, just maybe, we could dare to think in terms of a cure for CML.  In Bordeaux France (oo la la -  love the wine form there), 15 brave CML patients decided for reasons related to side effects with Gleevec that they wanted to try stopping the drug.  Dr. F. Mahon monitored them very closely.  8 of the patients relapsed within a few months, but 7 did not.  In looking through the charts he saw that the seven who did not relapse had been pre-treated with IFN.  He wondered if this might hold a clue to possibly thinking in terms of some sort of combination therapy.  He did a larger study, of 69 patients and the results from this were a bit confusing, as it showed that about the same number of patients who were either treated with IFN or not, relapsed, with a slight advantage to patients treated with IFN.  Newer work in this area is starting to point to patients who had a good stable cytogenetic response on IFN, or at least were able to stay on IFN for 18 to 24 months, as well as Gleevec and patients who  had a low sokal risk score as being more likely to achieve this type of solid remission.  Additionally, the length of CMR (PCRU) remission also figures in the scenario, and patients holding a solid CMR for 2 years or more have a better chance to not relapse after stopping treatment.

Since the results of the study from France were reported in 2005 so much has changed.  We now have three approved drugs for CML and about 5 other drugs in various stages of clinical trials.  Most importantly we have trial sites in Europe and North America looking into stopping TKI treatment safely for CML patients.  We are closer to the cure than we have ever been.  There is a trial in Michigan looking at combining Pegylated IFN with Gleevec and stopping the drug after two years of CMR (PCRU), early results form Europe with a similar protocol are quite hopeful.  Later this year there will be a trial combining Sprycel and Peg IFN.  And, by the way, thanks to a merger of Merck and Schering Plough, Merck has now fully entered the CML drug market as they have inherited Pegylated IFN.

In Europe at the present time we have heard that there are about 100 patients who have been monitored for up to 5 years after stopping TKI therapy.

We continue to learn much about CML and just recently one top CML expert confirmed that CML patients can look forward to stopping their drugs, safely in 2 - 3 years.

Two things that are of very important concern is the cost of the drugs and the side effects, which I have not spent much time on.  Not one of these drugs are entirely benign.  Some side effects are much more significant than others.  We have learned that even grade 1 and 2 side effects after time become just as debilitating as grade 3 and 4.  Long term drug therapy often leads to problems with treatment adherence not to mention the stress of paying for the drug on a continued basis.  The unfortunate downside is that patients who were being well serviced by the drug fall into a cycle of disease relapse that could be quite serious for them.  There have been significant backlashes, some patients have lost their employment directly because of the high cost of the drugs and what it has done to insurance program premiums.  Small employers are often forced to change insurance programs in an effort to stay ahead of dramatic increase in program premiums.  Other patients have been denied promotions and have lost opportunities to develop their career paths.  All of this is rather shameful.  We have developed drugs that takes a dangerous life threatening disease and allows most patients to live fairly normal lives, yet society finds a way to select, isolate and discriminate these people.

Thankfully, these drugs work so well that the prevalence of CML is dramatically increasing on an annual basis.  However, the newer drugs are being launched at twice the price of Gleevec.

Here is an interesting thought:  we still do not know what gives rise to CML, 80% of the normal population will test positive for the BCR ABL fusion gene, yet only a handful of us will go on to develop CML (1 in 100,000).  

We need to raise awareness of the absolute urgency of the situation.  We desperately need to open up more trials in North America that will allow patients to safely stop TKI treatment.

If you are a patient, and if you qualify, please seriously consider entering the clinical trials aimed at stopping TKI therapy.  Gleevec did not come to the market without important clinical trial data.  We the patients have an important role in our own futures, in our health and in the future of clinical trials aimed at getting us safely off of these drugs.  

We need to advocate for ourselves.

Friday, October 15, 2010

Cautious Optimisim

Well, it has been a solid month since I have stopped taking the 50mg daily of Sprycel.  As time goes by, I am beginning to feel better than I have felt in a very long time.  One little bump in the road, which had nothing to do with stopping the TKI, was a bit of a nasty flu in the past couple of weeks, but I am feeling much better.  

Yesterday I had my one month check up with my Doctor.  Hopefully we will get the FISH and PCR results within a week or two.  While I realize that we cannot base anything on CBC’s and blood chemistry reports, I have to say that my results from yesterday’s blood draw has me quite happy.  While I continue to be a little bit anemic, the most important part is that when I look at my mean Hemoglobin and mean cell hemoglobin concentration they are completely normal, and this has never been the case for me.  Additionally, my Eosinophils are in the low end of the normal range – which just may prove the point for me that I have been making all along.... I AM ALLERGIC TO TKI’s!  Actually, I am allergic to CML, but that is an entire different story ;-)

As for my White Blood cells, they are low at 3.4, but I would expect that as I had injected the Peg INF on Monday night.  I switched to injecting on Monday night as the next two weekends I am traveling for business...

For now, I am as the title of this post suggest, cautiously optimistic that this just might be working.  Why not?  It has done the trick for well over 100 patients in Europe so far, so why not me?

I have a few thoughts that I will be sharing via this blog in the next week or two, so stay tuned.  As well, I will post as soon as I have the FISH and PCR results.

Anonymously Yours,

Monday, September 27, 2010

Just about two weeks - Yeah!  What I cliche way to start this entry, but truth be told, it is about two weeks now, and this is still exciting.  Happily, not much has changed, other than I feel I have more energy, and I hope that continues to get better as the time goes on...

I would love to share some philosophical tidbits here, but there is none to share.  There is no new found wisdom, no  "awakening".  However, there is the dawning realization of what is happening...
In Europe there is more of this going on than we know about here in North America....
More people are being given the chance to be part in trials to try stopping drug therapy.
This clearly isn't for everyone, and despite what some expert say, the better and more predictable route to trying this lies with people who have had some exposure to IFN.
That is becoming abundantly clear and proof will be forthcoming in a relatively short time..
As each day passes, I am beginning to convince myself that this is for real...
TKI's have made all of this possible.  There is synergy between TKI's and IFN.  IFN gets a bum rap all the time, it shouldn't.  The main principle of action seems to be along the lines of  body, heal thyself   The conclusion in the CML section says: "These results suggest that IFN-{alpha} can induce CML remission by facilitating autologous leukemia-reactive CTL expansion"

I hope this is happening in my case, and all the other cases....

Stay tuned... PCR tests in Mid October with results to follow shortly after that...
For now, I am getting back to more running and other things...Trying to keep myself busy.  Feel like a five year old waiting for Christmas....

John Lennon said it so well:  "Life is what happens while you are busy making other plans"....

Saturday, September 18, 2010

New Beginning?

To say that I am not NERVOUS, EXCITED, SCARED, AMAZED, would be an understatement...

I can hardly believe that I am actually doing this...

This?  Right, well let me explain....The "this" I am talking about is kind of like jumping out of airplane and hoping like heck you've set your parachute right.  Or, maybe it is like setting off on an adventure and hoping the GPS doesn't malfunction.  But, it might also be like taking a walk out in space - and hoping the life line tether holds!  The point is that in all of these things, somebody had to be the first person to actually do them.  While, I am not the first to do what the subject of this blog is all about, we can certainly say, there aren't that many of us...

My curiosity was first peeked on the subject of what this blog is about, by some few scant reports, in peer reviewed journals I might add, that there were some occurrences of some patients suffering from CML, who were able to stop treatment and not relapse.  Some were able to hold their drug free remissions for years, even decades, others for not so long.

I can say I am a fairly informed CML patient.  You have to also consider that I have had conversations with many top notch CML key opinion leaders.  I am not bringing this up to say that in anyway anyone of them actually endorses this.  But suffice it to say, that true, while I am not in the confines of a clinical trial, this is how I chose to go forward with my own CML journey.

This blog is not about trying to convince anyone else about what you should or should not do.  There is no sales pitch.  This is a just a blog of human interest.  I have absolutely no way of predicting how this will all shake out in the end.    Along the way, I hope you will see that we can advocate for ourselves, but we have to educate ourselves.  We can weigh the risks and the benefits and, above all, clearly communicate with our primary health care advisors.

I hope this works out for me.  I hope I get to join the ranks of some few individuals (emphasis on the few) who have been able to enjoy (dare I use the word enjoy?) some years of drug free remission.

Note that I am not using the word cure.  It seems pretty clear to me that the original leukemic stem cell clone is probably still hanging around.  It could very well "re-start" the CML.  But I am hoping to buy some time on reduced drugs, and possibly even some drug free time of improved quality of life.

So come along for the ride, leave a comment if you are so inclined...

For Background about me, click on the "profile" link on the right.  For links to information and peer reviewed abstracts on the subject matter of this blog, please click on the link on the listed pages associated with this blog on the right.

Two days ago I stopped taking the TKI I was on (Sprycel) BUT, I will continue to take weekly injections of 90 ug of Pegasys.  The waiting and watching is on.  I will go back for monthly  PCR tests- opting to be very closely monitored.

It is important to say that I have had this discussion for quite some time with my health care advisor, who notes we are doing this, because, well quite frankly, I would do it anyway...Maybe he is right....But nonetheless, there is dialogue, there is follow up.

What do I expect to happen?  I really hope I can hold this response, CMR, and eventually lower the Pegasys.  And then?   Who knows?

So for now, it has only been two day's of no TKI.  Already the achy feeling, almost like a feeling of arthritis, has pretty much cleared up.

I like to believe that I am in recovery from CML, maybe we all are.

May we all be well and healthy!