I have been lurking on these forums for some time now and I first want to thank this community for sharing all of their stories and knowledge. It has been helpful to me and my family in gathering the information necessary to keep up with the ever evolving treatment options for CML and to also see all of the different scenarios that many folks are facing.
I was diagnosed with CML back in April, 2010 when I was 25 years old. Like many others here, I felt fine for the most part, just a bit tired. I went in for a checkup and upon reviewing some routine blood work I was immediately called into the hospital. I had a WBC of 370k and the general practitioner was really surprised that I was even able to move around like I was. That was the first time I had ever been hospitalized. Fortunately, I had a loving fiance (wife now) and loving family members that sat by my side as we ran through the entire gamut of tests trying to determine the cause. It was a lot of "what ifs" while we awaited the diagnosis, only knowing that it was likely cancer of some form.
Before beginning treatment I donated sperm (I had to leave the hospital without approval from my doctor) as we still plan to have children and some of the possible side effects of the Hydroxyurea they were going to put me on were fertility related. Once back, I began Hydroxyurea treatment to lower my counts while we awaited test results to determine the type of blood cancer I had. Once it was determined that it was CML, I was informed that this was one that recently had made some medical breakthroughs and what was once considered a 1-3 year life expectancy had evolved into much longer than that. It was then that the "what ifs" turned into "Now this is what we are going to do." I'm much more comfortable having a course of action and do not like being left to my own "what ifs".
I started on 400mg Gleevec and have been on that the last 2+ years. I've been fortunate to not have many side effects, just fatigue and some water retention for the most part. I reached CHR in just a few weeks and then reached CCyR in 9 months. My PCR hit its lowest point of -2.72 logs (1.1%) back in July, 2011. I kept hoping for the MMR, but never got to it.
My PCR is beginning to creep back up. I had my low point PCR in July,2011 (-2.72 logs, 1.1%), had another PCR in February, 2012 (-2.56 logs), and the latest PCR in May, 2012 (-2.40 logs, 2.3%). I am scheduled to go in for another BMB and a mutation test this coming week and we'll see where we go from here. Based on everything I've read here involving other folks and their stories, I have a lot of hope for a great future.
Thank you again to everyone that has had the courage to share. I'm sorry it's taken me so long. If there is anyone that has found themselves in a similar situation with rising PCR levels (I know that without knowing specifics on possible mutations it will be hard to judge) I'd be interesting in hearing about it. Your story may have some application towards my own.
Hi Josh: Join in with us intead of just reading all our responses. After you get your results of your BMB and Mutation Testing they might want to raise your dose from 400mg to 600mg to see if they can get things moving faster.
If they find that the Gleevec is just not a good drug for you to achieve what you need to do, then your doctor might want to switch you to Sprycel. It seems Sprycel is being used before Tasigna lately.
I have been on 400mg of Gleevec for 11 years, and I did get to PCRU 3 years after I started Gleevec.
You will do fine, they just have to see where your going with everything. Glad you posted to us.
Just keep in mind all that is known about the treatment of CML and how it works to beat this disease.
Let us know how your results come out.
The PCR error rate can be as high as 1/2 log. So your PCRs are essentially flat. This can sometimes occur and then often trends lower later.
Mutation tests for patients in CCyR (roughly lower than -2 log PCR) are not very useful, and your situation does not act like a kinase mutation. It acts like a "plateau" which can be caused by the TKI drug trying to kill off the more difficult to kill leukemic cells, which are higher in the cellular chain.
So your situation is not so unusual. But there is nothing wrong with switching drugs at any time for any reason if you wish.
I took Gleevec (400 mg) since June 2005. Between 2009 and 2011, I was PCRU. Since September 2011, I lost the CMR. Now, I am on a 'Plateau' like you (between -2.3 log PCR and -2.8 log PCR). I have a lot of side effects (extreme fatigue and others). My oncologist don't recommend now to increase the dose of Gleevec to 600 mg ( this dose may increase the side effects). I am treated also for atrial fibrillation and I take medication for this situation (Coumadin, Rythmol, Monocor).. It's another reason why my oncologist is afraid to change my medication (Gleevec to Tasigna or Sprycel ). Actually, I have a lot of stress. This is a possible reason why I lost the CMR,
Question Regarding, >>I have a lot of stress. This is a possible reason why I lost the CMR<<
Does your doctor think that you plateau d because of stress?
I would like to think, most people plateau, because of what Trey said, " It acts like a "plateau" which can be caused by the TKI drug trying to kill off the more difficult to kill leukemic cells, which are higher in the cellular chain. "
Along with that you can’t kill all the BCR/ABL. The DRUGS / TKI’S don’t kill as high up as the HSC, that is the original ancient stem cells, that has some kind of transcript error, that creates this whole mess. If the TKI’S killed all the was up to ancient stem cell, well the bone marrow would probably just make another defective HSC. The bone marrow factory is in a mess.
I go to a seminar every year sponsored by the LLS. A group of Blood Cancer Onc speak, then we get to ask questions. The doctor said you can take a dozen different labs and get a dozen different results. He also said as long as your range stays in a wave don't worry. It is when your labs continue to rise over a period of time. Yep just depends on which drop of blood sample they have to get. That is my understanding.
So we need a cure. I should say I think we really really need a cure, because we don’t know what the long term side effects of these drugs out. Gleevec been out since 2001 and will become Generic in 2015. I think Tasigna came out in 2007 and Sprycel 2009. Someone correct me if I am wrong.
Right now the only cure is a transplant. I have been following a few transplant this past few months and they are pretty nasty, no guarantees you will not have a relapse, or take medicine for the rest of your life, for other kinds of problems from the transplant.
When I was first diagnosed I met a lady my age (she had the transplant I think in her 40’s) who said, her doctor said she was truly cured after about 12 years transplant, her donor was her sister. I have met a couple of other success stories.
I would have thought they would have perfected the transplant by now, but in following some of the recent transplants, it is still nasty, tuff, long haul. It is a big gamble and lots can go wrong, but it is a chance for a cure, kind of like rolling the dice. Anyhow I wouldn’t even think of a transplant now, (64 years old) unless i was very young and in excellent health, a good donor, and had a very good caretaker. I think the aftercare of a transplant is extremely important. Keeping in a sterile environment and sterile food and have someone take care of you a must. If I was going to do a transplant I don’t think I would wait to far down the road where I had developed other problems.
Every time some one mentions the plateau, I also am reminded, that even if you fly under radar, you can a million + CML cells, as the PCR is not sensitive enough to see all of them. I think each of the TKI has their own demons, but it is good that we have them, if one isn't working, we have other options, then there are the clinical trials.
Some people think there is soon to be a cure. I don’t know, I guess I’m a pessimist, in that my friend who has had CLL says MDA has been telling her, close to the cure, that for 16 years. She takes chemo every now and then, but she developed breast cancer. So I guess I am glad I have CML, so I do have to do the chemo, although when I was diagnosed I was told CLL had a much longer survival rate, but I don’t think that is true anymore.
I have taken Gleevec since 2005 and my counts stay near normal, which I am glad, because I hear of some need platelet and red blood cell transfusions. I have never had a transfusion, but that would scare me. So I do keep an eye that my counts don’t get to low. That’s another reason I don’t worry about PCRU most of the time to get there, not always, but most will have real low counts. Again there are others that take the other drugs and doing well. I guess you never know how you will do unless you switch, unless your doctors think it is a bad ideal for you.
When I was PCRU for 2 years and I return to a Plateau (between -2.3 log PCR and -2.8 log PCR)., my
oncologist said to me that it's probably the stress, Since one year, I have a lot of stress. Some day, I think that I will explode. Today I have an irregular heartbeat. I
had recently a bad headache in the lefft side for 5 months. SInce one year, I had also pain on my heart.
“When the body is under stress, it releases hormones -- such as adrenaline and cortisol -- that, in the long term, can cause your immune
system to become suppressed.… Scientists believe that this immune system suppression may make the body more
susceptible to cancers such as lymphoma.”
Extract of The Effect of Stress on Blood Cancers
“Any stress that is long-term and brings about long-term anxiety is considered to be bad for our
immune systems (and general health). Anything that turns your world upside-down is bad stress.”
Extract of Stress is good for your immune system
Thank you for taking the time to share all of the information that you have. I do have an update for where I'm at and would like more input if anyone has any.
After continuing on Gleevec for the last 3 months, my counts have continued to increase. I am no longer in CCyR and am at a -1.83 log (increased from my low point of -2.73). However, on a more positive note, the mutation test turned up no mutations and I am still in CHR.
I will be starting Sprycel this week. Though I am fearful of experiencing new side effects, I'm hopeful that this will get things turned around and heading the correct direction again. It's quite the rollercoaster ride. Has anyone had a similar experience? What kind of side effects are common with Sprycel (different/similar to Gleevec)?
Does anyone know what can cause the drastic turnaround in Gleevec response? Dosage/lifestyle didnt change, so it's a little concerning that it would start heading in the wrong direction seemingly so rapidly after such a strong initial response.
FYI - I will also be walking at the Light the Night walk this coming weekend in Santa Rosa, CA, in support of you all and our journey through blood cancer
Kinase mutations cause about 1/3 of Gleevec failures. The others are caused by a number of issues, some defined, some not. Generally speaking, in your case the CML outsmarted the Gleevec after a while. This can happen during the first couple years after diagnosis, and after that it is extremely rare.
Gleevec can stop working when leukemic cells find alternate paths to survive, generally during the first couple years after diagnosis. This is normally through the SRC pathway when they find a way to over-express the enzyme LYN. But this is why Sprycel works well for those who fail Gleevec, since it inhibits the SRC/LYN pathway. And there is no commercial lab test that can show the SRC/LYN issue. Other reasons for loss of response include intrachromosomal amplification of BCR/ABL, which is caused by an overactive variant. Other reasons are not well understood. But the 2nd generation TKI drugs work well for most of these issues.
I lost Gleevec response at 1/2 years. Though Gleevec drug interactions don't list drugs used for acid reflux, my lost response coincided with my taking Pantoprozole. I've since found a few studies that conclude that these drugs shouldn't be taken with Gleevec. As far as I'm aware this is still not considered a no-no by the makers of Gleevec. In any case, after hitting a low of 3.99 log, I fell to 2.33, switched to Sprycel and then Tasigna. I'm now at a 3.34 log reduction.
Thank you both for the information. I'm hopeful that Sprycel will be the answer.
I've also been offered the opportunity to take part in the Ponatinib trials (due to the loss of CCyR), however I'm thinking that I should exhaust other options before joining a trial. I've heard good things about the trial, but would hate to jump to that when something longer tested is available and may provide a solution.
Do you all have any recommendations? Have others jumped straight from Gleevec to Ponatinib without trying the other TKIs?
Thank you again for the insight. Just as soon as I start to take a step forward, it feels like another step backwards with CML. I just feel incredibly lucky that there is so much information about the disease, and knowledgable folks such as yourselves.
Hi, don't give up hope. Our numbers jump around and we have many options. I was on Gleevec for 9 months lost response when to Tasigna had a problem then went to Sprycel and had reached pcru just last test . On only 50 mg since my counts drop and I can't handle a full dose. This last test a couple weeks ago went up to .128 so makes me nervous but my onc isn't concerned and says lets just confirm with the next test in 3 months I'm okay with that I think my numbers are just jumping around. So don't worry Sprycel is one strong pill and works very well. It's my perferred TKI.
Thank you for the information. I have been fortunate enough to have solid health insurance so the cost of these procedures/medications hasnt been nearly as stress inducing as it is on some other folks. I will be going with Sprycel and I will keep this post up to date with progress. First test should be at the end of the month.
I wanted to provide an update on this as it's been about 5 months since switching over to Sprycel and folks in similar situations may find some helpful information here.
After my switch to Sprycel, I had my first follow up test ~2 months after starting. That test showed that I was PCRU (which was pretty shocking and unexpected, but very grateful for it). I will be getting another set of results for my ~5 month tests here shortly to see if those results are maintained.
I haven't really noticed any side effects with Sprycel that have been worse than when I was taking Gleevec. I'd say in large part the side effects have been milder with Sprycel (or I've just become accustomed to it). I had some skin thinning with Gleevec, and that seems to be quite a bit better with the Sprycel.
At the same time that I switched to Sprycel, I also stopped taking the Pepcid that I was prescribed as it was noted to conflict. During my time with Gleevec, I would take the Pepcid and Gleevec at the same time each day. Gleevec's pharmaceutical notes do not list any conflict with antacids, but it's something to note. If I were to have continued on with Gleevec, I would've tried stopping the use of the antacids (or at least spaced out the time they were each taken).
I started on Gleevec almost 3 years. Had a good reaction and got a -2.7 log reduction. Over the course of the 2.5 years on Gleevec the log reduction got progressively worse. Eventually it reached a -1.28 log reduction at which point I switched to Sprycel and after 2 months achieved PCRU.
I will write back when I get the secondary results to either reaffirm the PCRU or to get a new number.
Thanks again to everyone for the information and advice. It's great having so many knowledgable, caring folks in the community.