30 replies to this topic

[Nats]

Hi,

I was diagnosed with CML in June 2009.  I've been on Gleevec, Sprycell and Tasigna.  The illness was suppressed for all this time but has flared up again.  My haematologist says that I am part of the 30% of patients who become resistant to this group of drugs.  The options I have for treatment going forward is a bone marrow transplant.  I only have a sister who is being tested now as a donor - waiting for the results.  I can take a drug called Bosutinib which was only registered in the US in Sept 2012 and given conditional marketing in the EU in March 2013.  It is still in the trial phase in my country.

My questions are:

Has anyone had a bone marrow transplant and can you share you experience with me.  I am petrified of the whole procedure - I have not had chemotherapy or a transplant before!

Is anyone on Bosutinib and if so, let me know the efficacy of the drug and also what side effects you've experienced.

Thanks,

NATS

[tiouki]

Hi Nats,

I'm very sorry that you are going through all of this.

I'm not an expert but what is very important is that you see a CML expert before taking this kind of decision (i don't know about your hematologist but anyway 2nd opinion is always good in this case, because these treatments are new and only specialists know perfectly the different options)

Do you know what was the percentage of blasts in your blood at diagnosis, and now? And the blood formula?

Bosutinib is a new drug but it has been very successful in the latest trials. The CML specialist in my hospital told me that it causes diarrhea the first weeks, but it's a transient side-effect and knowing this, results are very good now. (comparable with sprycel and tasigna, with few side effects and little toxicity).

Also there is another drug, ponatinib, which is effective against mutations of the leukemia which can make it resistant to the 3 drugs that you tried. You have to have a mutation test to know if this is the case for you.

So maybe in these 2 options there could be one that helps you more. But it depends on what is happening exactly, and the blood result.

Pierre

[Nats]

Hi Pierre,

Thanks for your reply. I am seeing a CML specialist.  I was referred to him by my Haematologist.  I did a bone marrow aspiration last week and they are going to test for mutation and blasting, etc.  Still waiting for those results.  The PCR test (don't know if this is what you are talking about) was very high at diagnosis.  The 3 drugs managed to keep it at less than 0 but it has now climbed to 6.9 which is very worrying.  That is why i was referred to the specialist haematologist who deals on a daily basis with bone marrow transplants.  We have applied to the medical council here for me to get the Bosutinib.  I can handle the side effects as long as it works!! 

Anything you can tell me on bone marrow transplants.  It sounds like such a huge challenge and I am really very worried about that.

Thanks,

Nats

[tiouki]

Hi Nats,

Actually i don't know much about transplants sorry... but i'm sure that some people on the board will give you some insights on how it goes.

In your case, the bone marrow results will be the most important. From 0 to 6.9% (if i assume it's PCR) is worrying, but in this range the bone marrow test will tell you much more. (ratio of cancerous cells, mutation or not?)

But i must say i'm surprised that they did'nt tell you about ponatinib (the only effective drug against the T315I mutation...), and surprised that they say that 30% people become resistant to the drugs. For Chronic Phase Myeloid Leukemia (blasts at diagnosis < 10%), the numbers are MUCH LOWER actually (less than 5%), and in this group the need for transplant is quite exceptionnal now. (which is different if you had more blasts (> 10%) at diagnosis though).

Actually i think that we would need more information about your disease (blasts at diagnosis, blood counts, PCR tests, your age, treatment duration, why did they switch you to the other drugs) and this would also help people here to give you more accurate information about the transplant option.

Good luck with all this
regards
Pierre

EDIT : oh and of course i think there is a transplant forum, and you will find a lot of information here :

http://community.lls...e/164367#164367

and especially there

http://community.lls.org/docs/DOC-1375

[CallMeLucky]

There are going to be very few people on this forum who had transplant since the TKI drugs have been very effective for many people.  There is a transplant forum on this site and you should post a question there with regard to transplant.

As far as CML drug therapy, you need to understand what the underlying issue is.  That number of 30% become resistant seems awfully high.  While it may be that many who initially become resistant to first line drug like Gleevec, most respond well to other drugs.  With the second and third generation drugs transplant is often last resort.  You need to know what phase you are in, what is result of mutation analysis and then based on that make a decision.  You can certainly try bosutinib but you should also be looking into ponatinib.  Ponatinib is a broad spectrum inhibitor that has shown the ability to overcome every known mutation.  Assuming you are still in chronic phase and dealing with CML you have more drug options.  If you have moved into accelerated or blast phase, then that would push the transplant issue, but until that is the case you should be planning for transplant only as a backup and pursuing other drug options.

[hannibellemo]

NATS,

Sorry for the situation you find yourself in. I will only add that if the mutation is T315i there is no reason to try Bosutinib you should go straight to Ponatinib (Iclusig) as that is the only TKI effective against that mutation. There are a few people on this board who are using it and they may be able to give you more information.

That said I would still try the TKI before I rush into transplant - there is no going back once you do that and it's not necessarily a cure (I believe they are still prescribing TKIs after the transplant) and there can be all sorts of issues.

Good luck!

Pat

[Trey]

Your resistance seems to be at a rather low level assuming your PCRs are International Scale.  You would still have a roughly 2 log reduction, which is approximately CCyR.  True resistance would be a clear loss of CCyR and PCRs higher than you have experienced. 

Bosutinib would be a reasonable choice.  Also, your previous posts have said you started on Gleevec and did very well, but switched to Sprycel for unstated reasons.  Some people do better on Gleevec than the other drugs, and Gleevec can overcome some forms of resistance the others cannot (this may sound odd to some because we are told the others are "stronger"; but that does not tell the whole story).  So you could re-start Gleevec as an option. 

This link was posted above -- you will want to review it to understand the transplant process and associated issues such as HLA matching, sibling vs unrelated donor BMT transplant, etc:

http://community.lls.org/docs/DOC-1375

[momruns]

Greetings,

I tried Bosutinib as drug #3.  After 6 days of massive diarrhea I broke out in a total body rash.  I was switched to drug #4 Ponatinib.  We will see about this one, fingers crossed.

Loreta

[Melanie]

Sorry you're in this scary situation. Don't have much to add except to only consider transplant as last resort. I was dx in May of 2011 and my lowest PCR test is 2.35 in lab #1 and a 1.89 in lab #2, all IS. It has gone from 2.35 to 12.77 in two months time (mainly due to drug breaks) and I still have 3 PH+ chromosomes. As concerning as the ups and downs are, unless you're in accelerate or blast stage, please consider sticking with the TKI's and do all the pre testing and planning for the transplant, but keep it as the back up plan. That's what I've done and it's has kept the stress level down.

I'm actually on Bosutinib now (only 300mg) and the only real side effect I've had to deal with is the diarrhea, which is manageable at this dosage for me. Due to other issues, they may be switching me to Ponatinib soon which is always another option. 

As long as there are TKI options out there and I can stay in chronic phase, that's the path we've chosen. The fact is that no one really knows how long you're safe at different low levels of disease. I may never make it to CCyR, but even so I may live many, many more years and die of something else besides CML.

Blessings,

Melanie

[Tedsey]

Good luck Loreta!  Hope this one works well for you!

Teds

[alexamay09]

Sorry to hear your news. I underdtand your feelings. I am scheduled to meet the transplant team in Glasgow on 29th for preliminary stuff. I can trll you that I will leave that option as a last resort and hope that the new drugs becoke available in the UK. I was diagnosed a year ago and they thought I was in accelerated phase. They couldnt confirm it but I had around 10 per cent blasts. My recent bcr abl was 3.24 per cent down from 12 at 6 months. I am cautious and aware that I could lose response. If I were you I would resist bmt till no other options remain.

Alex

X

[Tex]

I'd suggest you drop by the transplant forum for information on dealing with those.  They are scary.  But when they become necessary, they're survivable. 

They're pretty much last resort type medicine, meaning that if there's any way to try something else, it's usually (but not always) advisable.  But I've been living with one for over nine years and all in all I'm doing pretty well.

I hope you don't need one.  If you do, we're over there to help you through.  It's also a good place to just learning about them which might help you be a little less scared, especially now while it's in the talking stages.

Blessings

[Tex]

This overview is designed to be a layman's approach to help leukemia patients get started understanding the difficult issues involved with a Bone Marrow Transplant (BMT), also known as a Stem Cell Transplant (SCT).

This is the first sentence in your report.  BMT and SCT are different, though very similar, procedures.  They are not used interchangeably, however, by anyone...not even laypersons.

If your first sentence contains wrong information, perhaps you might reconsider recommending it until such time as you are sure of your facts. 

There is a correct, detailed and easy to read description at Be The Match's web site.  I would begin there to understand the process.  Here's the link to the description.

[Trey]

Both terms refer to transplantation of hematopoietic stem cells, so the terms have come to be used interchangeably when describing the procedure.  The technical distinction regarding sourcing of stem cells from the donor (peripheral blood vs actual marrow) is irrelevant to the recipient.  My posting is designed to explain issues in clear terms, not confuse with irrelevant information.

Quoting from a major transplant center:

"Whether you hear someone talking about a "stem cell transplant" or a "bone marrow transplant," they are still referring to stem cell transplantation. The only difference is where in the body the transplanted stem cells came from. The transplants themselves are the same."

http://blog.dana-far...the-difference/

[Tex]

I don't care what you've read, no doctor I've encountered uses these terms interchangeably.  And I've met a heckuva lot of transplanters.  Neither do patients,, caregivers nor family members.  Yes, both terms refer to stem cell transplantation but so do "haplo" and "cord."  You never see those mixed up or blended in. 

Haplo is the same process as a SCT but with a different type of donor (usually non-sibling, related [parent or child most often], 5/10 match, etc.).  Cord transplants get stem cells from umbilical cords.  Ultimately, all transplants get stem cells into the patient's body the same way.  Why not lump these in with the others?  Let's call them all "Mr Smith."

By the way, "the only difference is where in the body the transplanted stem cells came from," is not entirely accurate on it's face either.  Donors to BMT's are knocked out and the cells are harvested directly from the marrow.  SCT donors are given a series of shots (Neupogen is what they're using now, I think) ton increase the population of t-cells.  Over 50 years, that could present a significant difference in long-term outcomes as no one really knows what Neupogen treatment does to a body over an extended period of time, if anything. 

Further, there are reasons to prefer one over the other as there are thought to be differences in the time before engraftment begins and in the severity of GVHD suffered by the patient.  Basically, Dana Farber dumbed it down a touch too much, I guess.

Your first line is technically incorrect and I stand by that statement.  In a technical treatment of any topic, that is the worst kind of incorrect.  Compared to the far more thorough and accessible work done by the NMDP (Be the Match) it's also a bit superfluous.  Heck, just go ahead and refer them to the piece you read from Farber.  If you think their information is worthy, why recreate the wheel? 

If the goal here is to help people find an introduction to the basics of transplantation in order to help them sort things out, wouldn't it be better to link them to the superior piece of work put together by professionals in the discipline?  I do not see the advantage in linking them to an amateur piece that is harder to read and has incorrect information.  We are here to help people, right?

Basically, they say to write what you know.  I trust you know CML. 

[cfoley1215]

Nats,

I know nothing about transplants, other than I wish they actually were a good choice for a cure. But from what I understand, the mortality rate is rather high.

I do, however, know Bosulif (bosutinib). As well as Gleevec, Sprycel, and Tasigna as I have been on them all. Sprycel and Tasigna went toxic on me, leaving me with Gleevec again which practically puts me in a coma. So, I was glad to hear that Bosulif had been approved and I went right on it.

Side effects:

Diarrhea and more diarrhea. It is not limited to just the first couple weeks. When I started it, the diarrhea was so bad that we actually switched to every other day for a month, then went up to 2 days on, one off for a few weeks, and then every day. Now I only get diarrhea 3-4 times a week. Except when I'm having a bad week and get it every day again.

Abdominal pain is also present. I seem to have 2 times. Lower abdomen pain that is probably related to the diarrhea (gas pressure or whatever) and upper abdomen pain that could also be gas pressure or could be who knows what. The pain isn't all the time and isn't bad enough to make me cry or anything.

Anemia. This is the first med that I've needed an iron infusion every time I go see my doctor (which is currently every 8 weeks). It has ramped up to where I was only feeling good for the first week after an infusion and then I would start getting more and more tired. Taking the standard dose of iron pills that is prescribed for anemia (3 pills a day) does not agree with me (I've been on that at times in the past). Would be nice if it would constipate me to counteract the diarrhea, but nope. Iron pills also give me diarrhea. I'm currently taking prenatal vitamins as an experiment. They have more iron than a multivitamin, but less than 3 straight iron pills a day. The one my sister picked up for me also has an omega 3 pill. She tells me I'm looking much better just in the week since I started them, so hooray.

I believe in the first couple weeks I also had headaches and the usual bone pain, but all of that subsided. Those seem to be pretty common to all of these meds in the first couple weeks.

All in all, despite the diarrhea (such a huge pita), I'm pleased with the Bosulif. It's definitely better than the Gleevec in terms of side effects for me.

Note that I have been pcru on all meds. I've just had bad luck with side effects. So I can't speak to how you will respond to the Bosulif in that way. However, if your bone marrow doesn't show a mutation, you should give it a try.

Colleen

[Tex]

cfoley1215 wrote:
Nats,
I know nothing about transplants, other than I wish they actually were a good choice for a cure. But from what I understand, the mortality rate is rather high.

Still, the mortality rate is much higher among those who are advised to get one and don't.   It seems as if more and more people are surviving them every day.

[alexamay09]

I saw doc today for consultation about transplant. She explained everything in detail and plenty of nasties to worry about, even with reduced intensity conditioning.  However I apparently have a 10/10 match from a strapping young man, so its there in the background.  Interestingly she did suggest my previous radiotherapy might have been a factor in my cml. My cml was behaving quite aggressively but doc was happy with my sprycel response and doesn't expect me to rush into any decision about transplant. Apparently they have a cml patient with 100 per cent bcr abl who refused transplant and is feeling well. They have done 12 in the last 7 years. Of those 2 died. Definitely something that I hope stays on the back burner!

Alex

Xx

[Tex]

alexamay09 wrote:
They have done 12 in the last 7 years. Of those 2 died. Definitely something that I hope stays on the back burner! 

Who's done what 12 times in seven years?  That would be a sparkling survival rate if you're talking about transplants (83%).  But that would also be a terribly inexperienced group.

[alexamay09]

Hi Tex

Was a bit overwhelmed with stats but hereis what I picked up. 12 patients have undergone transplant for CML in past 7 years. This is at the Scottish treatmentcentre in Glasgow.  10 out of the 12 are surviving post 5 years.  I was told that over 30 per cent relapse but are treated with donor lymphocyte transfusion. They end up with about 70 per cent being free from CML long term but of course there are complications such as acute, and worse, chronic GVHD. She said the chance of chronic GVHD was less because I have a strapping young male donor who is a 10/10 match. All in all it will still be a last resort, but when its the last key on the keychain I would probably take the decision to proceed.

Alex