I am a female AML FLT3+ patient in my mid-twenties, and am seeking opinions on potential treatment options because my leukemia was found to have relapsed at my six-month post-BMT biopsy.
I was diagnosed with AML, FLT3+ in August 2011. My induction chemo achieved a remission. I underwent a fully ablative bone marrow transplant in October 2011. The transplant team where I am being treated (a Top 5 center in the U.S.) selected my mother -- a half-match -- to be my donor. (The team elected not to even check the national registry, and although my brother was also a half-match, the team went with my mother, who is nearly 70 years old, has had three children, and has had polio.)
I have never shown signs of GVHD. After the transplant, my 90-day biopsy was fine. 100% donor-produced marrow, 0 blasts. However, at my six-month biopsy on April 16, 2012, I had fallen to 80% donor marrow, and there were 15-50% blasts in the marrow.
At this time, in order to get to remission, I have begun a clinical trial that adds a study drug to the chemo in order to raise counts and bring the leukemic cells out of the marrow and instigate tumorlysis. I will be admitted on May 8 to begin chemotherapy (MEC + Vorinostat + study drug).
I am seeking opinions regarding the best course of action after remission is achieved (if at all). The team here is pressing for a DLI from my mother. I wonder, however, if a mini- BMT from a matched unrelated donor -- or anything else -- would be preferable.
Earlier this week, a search of the bone marrow registry was initiated, and seven potential donors were found to have at least a 90% chance of fully matching were found, but the team here halted the secondary screening process when they decided on the DLI. Additionally, this team has made no mention of any other therapies, such as vaccines, or other drugs, such as Sorafenib, that are sometimes utilized in cases like mine.
I would truly appreciate any thoughts or recommendations that you may have. Thank you so much for reading my summary of my situation.
I have a lot of questions about the decisions that were made. Why would they select a half-match without looking at the national registry and then the international registry. While it may be the top 5 centers in the US, I'd question their decision making process. The next question would be the choice of an almost 70 year old donor over your brother.
I think it's time to seek the opinion of another center. Contact the Hutch (fhcrc.org) or MDA in Houston. I think it's better to get an option (or two) from other experts in the field.
Let us know what happens.
I contacted the Hutch and have what I believe is good news. Although I am currently undergoing induction at Hopkins for the relapse, I'll be able to transfer out to Seattle for a clinical trial they are running there IF this chemo achieves remission.
The trial at the Hutch involves a mini-BMT from an UNRELATED donor along with AC-220, which is a FLT3 inhibitor. Even though I had already made contact with two oncologists at the Hutch, it was actually a FLT3 specialist here at Hopkins who made me aware of this specific trial and recommended it over the DLI.
Although it was a relief to receive the second opinion AND have it confirmed by an oncologist here, I remain nervous: what if the DLI had been the right path? What if the second BMT doesn't work? What options would I be left with? Those are, I guess, the tougher questions to which there are no answers.
The primary goal now is to get to a full, sustainable remission. And it's worth noting that I erred in my original post: this chemo cocktail does NOT include Vorinostat! It's just MEC and "MDX", the study drug. Oh well.
The secondary goal is to stay on top of the folks here at Hopkins to make sure they provide the team in Seattle with the records and testing that THEY will need in order to find me a match in a short timeframe. I'm disappointed to say that the Hopkins team has been less than helpful in providing HLA typing/records/progress on the registry search/etc. to Seattle.
Thank you so much for your response to my post... and I will do my best to keep everyone apprised of how things are going!
I'm glad you contacted the Hutch and you have options. The purpose of the DLI is to kick off GVHD. Since you didn't have it before, I'm wondering if the DLI would produce it the second time. There's no way to no for certain which option is better so just gather all the information you have available and make the decision based on that. The research at the Hutch is top notch so you can rely on them.
Glad to see you over here. I think Kelly raised some of the same issues I had for your post on the AML forum. The decisions just seem silly. I always try to expect the doctors have information I don't have and certainly know what to do with it far better than I...if/when I even understand it. Still, these aren't traditional calls.
Thanks for the recommendation that I post over here! Egal's post, just below, at least confirms that I'm not the only one out there on whom these nontraditional calls were made. The team here maintained that their priority was "speed to transplant" - and that they felt I'd achieve a more favorable outcome if I went to transplant quickly (and the process of testing and transplantation from an unrelated donor can take longer). Unfortunately, that provided no comfort at all (not merely because the transplant failed!) because one of my fellow patients here was diagnosed a month before me, and received a transplant from an unrelated donor a week before my transplant. So my haplo-match saved us exactly three weeks. Lovely. Oh, and she's still in remission
In short, I'm with you... I always expect the doctors to have more information than I do (and, well, they do)... but at this point I'm in the "these boots were made for walking" mode. So, as I described in my post in response to KyGuy above: I'll be off to Seattle IF I get to remission with this induction round!
I'll do my best to keep you posted,
I have a 39 year old daughter who had a similar development of her disease. In short, she was diagnosed with AML M4Eos with FLT3-TKD mutation more than 3 years ago.
During these years, she has gone though several treatments and we have got some experience with different medications and cures.
First: I believe the reason for the hospital using your mother as a donor is that the match was good enough. A family donor is regarded as preferable if the match is OK. As you have had no GVHD, this is an indication of a good match. With my daughter the first donor was her sister, and no foreign donor was sought for (She also had no GVHD).
Second: A DLI could be a good treatment for you, especially if the treatment you are on now could bring the blast down before DLI (<10%). There are new DLI-protocols appearing now where DLI is combined with medication, for example Vidaza, some with very good results.
If the DLI don’t work, you could have the second transplant later.
Third: Sorafenib might be a helpful medication for you since you have the FL3-mutation. After her relapse and DLI, my daughter was put on Vidaza, which worked fine for a few months. When the effect seemed to go down, Sunitinib - a drug with much of the same effect as Sorafenib – was added, and this combination kept her going for a year. Then she was transplanted for the second time in Germany, with a very well matched foreign donor. She relapsed after three months, and is currently on Sunitinib, Vorinostat and Cytarabine (for 7 months now).
We are from Norway, but I would recommend Seattle/ Hutchinson, as we got some very useful advice from them before my daughter’s second transplant.
On the other side, I agree with some saying that the clinic might be interested in having you in one of their clinical trials, and that a follow up with DLI would be better for you at this point.
Thank you so much for your thoughtful and informative response! I am sorry to know your daughter has been through such an ordeal, but I hope she is doing well now. Does the combination of Sunitinib, Vorinostat, and Cytarabine appear promising, or something she can stay on long-term if needed?
Your input regarding some doctors' preference for a family donor does make sense; I am just sorry that these transplants haven't worked for your daughter or me. In my case, as it was a haplo match, my oncologists wanted some GVH to manifest, because they believed that would indicate that the graft would also fight the leukemia. Unfortunately, I had none -- and the graft did nothing to fight the returning leukemia.
Your recommendation of Seattle/Hutchinson was right on point! I have contacted them, and will actually be able to transfer there for a clinical trial IF the induction round I'm currently undergoing achieves remission. The trial will combine a mini-BMT from an unrelated donor with AC-220, a FLT3 inhibitor. Even a FLT3 specialist here at Hopkins spoke highly of the trial and felt it would be promising for my case.
What I don't know, however, is what my options will be (if there are any) if I relapse after the second transplant. In your daughter's case, did they consider a third transplant attempt? DLI from the donor of the second transplant? I'm just not sure what people do at that point... and the uncertainty frightens me.
Thank you again for your kind response. I will keep your daughter in my thoughts.
We don’t know how long my daughter can stay on the combination of Sunitinib, Vorinostat, and Cytarabine, but for the moment, this combination is the best we have found so far. We are continuously looking for other combinations. The medications keep the disease more or less stable, but my daughter will die in weeks (or a few months) if we don’t find something better.
A DLI treatment was planned for my daughter before she got the relapse, but the time before the donor was available took too long, so by the time everything was ready, the chimerish showed no trace of donor bone marrow and the DLI was cancelled.
Yes, a third transplantation was considered, but the problem is that we cannot get the blasts down far enough. She currently has a blast percentage of 80 in the marrow, and we must have it down under 10%. She is also very weak, and we are not sure she has any chance of surviving a transplant.
Good luck with your induction round. Beware that even if you don’t achive a remission, a transplantation might be possible. My daughter never had any remissions after her first BMT, but even then, several clinics (including Seattle/Hutchinson) offered to do the transplantation.
I'm not sure if it matters or how much, however, if you do the DLI and it fails, the smaller transplant will still be available. On the other hand, if you do the SCT, the DLI might not matter.
So the question becomes, "If the DLI is all that's needed or is the more effective treatment, do you want to take advantage of the now?" Then again, the transplant doc at Hopkins thought you should try the Hutch's plan. That's a tough choice but I think I would go with the doc. That's not a recommendation, I don't know what it is.
The bottom line is that we ultimately have to make a choice which is about the same as picking up a pair of dice and giving them a throw. I mean, that's the same even for those of us who are only being offered on option...because doing nothing is always an option, too. I was "lucky" in that I relapsed days before my SCT was scheduled. I knew that was my only reasonable course of action. But most of us don't even know that.
I guess I'm talking to the choir here. You've been through that already yourself. I just want to call it back so you might feel more comfortable having to make a decision. I believe we all know the right course to take in our guts.
That is indeed the question! I'm encouraged by the fact that the FLT3 specialist at Hopkins recommended the Hutch's plan. Furthermore, stories like that of Egal's daughter remind me that each treatment attempt does weaken the body. And as my doctors here have said, each relapse makes it less likely that I will be cured.
I want to try the Hutch's plan, and will do so if all goes as planned after this chemo round. The question that I still carry is this:
Has anyone ever been "cured" by a second BMT, after a first BMT and subsequent relapse?
I agree with your decision to pursue more aggressive treatment in Seattle in lieu of the DLI. And I hope you have already started the meds targeting FLT-3.
We remain pleased with our haplo experience at Hopkins, even though my husband's disease (T-cell NHL) recurred four years post transplant. He quickly received a DLI, and everything was great for three months but then the disease recurred with a vengeance.
(just a reminder--it's usually quite simple to obtain a DLI from your haplo donor. A DLI from an unrelated donor may be quite complicated)
He was not offered the option of a second transplant, most likely because there is now a drug for T-cell NHL that wasn't available five years ago. So his lymphoma is now managed like a chronic illness, with weekly IV chemo & unfortunately, the side effects. Emotionally, it was much better when we were focused on a cure.
So that's why I support your decision Just keep poking the administrative folks at Hopkins to share the info with the Hutch--I had to send multiple emails re the DLI
I'm sure that there are folks out there who have done well after a second transplant--perhaps you could start another discussion using your question, Has anyone ever been "cured" by a second BMT, after a first BMT and subsequent relapse? as the header? The entire board is so active that messages can quickly get lost, especially for people who only check for messages intermittently. And people who are "cured" often move on & check in rarely, if at all.
All the best to you!
Take care & love life,
It has been a long time since I posted, but I wanted to wait until I had results from my first round of treatment (to address the relapse), an established plan for the next round, and more info on my planned transplant. So here I am! And I even have a couple of fun anecdotes. So here we go.
In April, I relapsed at the six-month mark after my haplo transplant from my mother. After really pushing for a DLI, my doctors at Hopkins identified a trial available in Seattle that would involve a second transplant, this time from an unrelated donor, with AC220 to follow the transplant. AC220 is the best known flt3 inhibitor, so I was really excited about this opportunity. More about the transplant + AC220 trial here: http://clinicaltrials.gov/ct2/show/NCT01468467?term=ac220&rank=5. But first, we had to address the relapse. More about AC220 here: http://bloodjournal.hematologylibrary.org/content/114/14/2984.full
In May, I had a five-day round of MEC chemo (Mitozantrone, Etoposide, Cyterabine) combined with a study drug called MDX that inhibits the CXCR4 chromosome. This was a clinical trial protocol, and you can read about it here if interested: http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01120457. I'm amazed to report that I had absolutely no side effects to the chemo (other than partial hair loss) and felt great the entire time.
Going into the trial, I had 90% blasts in my marrow (none had reached my peripheral blood yet). Around Day 28, when counts were beginning to come back, I had a bone marrow biopsy that was pretty hypocellular, so I had another one on Day 35. It showed 10% blasts in the marrow. (Here's a fun anecdote: I had a biopsy at Hopkins on a Monday, then flew to Seattle, then had another one there the next day. OUCH.)
Throughout the last two weeks, the Seattle docs (who are providing input because I'll ultimately be going out there for my transplant) and my current Hopkins docs have been exchanging ideas on how to get me down to a stable CR (0% blasts, with full count recovery) so as to get to transplant. Ideas tossed around included:
- Sorafenib alone
- Repeating the MEC + MDX protocol
- MEC + Sorafenib
- AC220 alone (here is the info on that clinical trial: http://clinicaltrials.gov/show/NCT01390337). We decided against this one because having taken AC220 would render me ineligible to receive AC220 after my transplant... which is when the AC220 would be of most use to me.
- Repeating the MEC + MDX protocol, but taking Sorafenib secretly -- a violation of the protocol that one doctor felt would actually be in my best interest. Another fun anecdote: I was all in favor of this approach, but the doctors decided against it because they (in addition to being shocked at the ethical consequences of violating protocol) were concerned about the potential of toxicity.
So after a LOT of hemming and hawing, we settled on MEC + Sorafenib. Five days of MEC begins today, then on Day 4 of the MEC, I'll begin a 7-day course of Sorafenib. (They don't administer Sorafenib before chemo or on the first three days of it, because Sorafenib is a cell cycle arresting agent, and if they stop or slow the cell cycle, the chemo will be significantly less effective.) While counts are depleted, nothing will be administered. Then, if and when counts begin to recover, we'll resume Sorafenib alone, and HOPEFULLY be able to rely on that alone until transplant.
The doctors are concerned about increased toxicity with the Sorafenib + MEC combination. Specifically, they're concerned about GI tract and liver toxicity. But we'll wait and see, I guess. They are also concerned that my counts just won't recover due to the Sorafenib addition. My counts have consistently bounced back by around Day 28, and the doctors are warning me that I should expect such a robust count return this time. But we'll wait and see about that, too.
Let me know if you have any questions, etc... or suggestions!!! Those are ALWAYS welcome.
No suggestions and no questions. This conversation is so far out of my range of experience I'm just shaking my head.
That is weird about the doubled-up BMBs. I had two in one sitting once because they didn't strike oil the first time. Not fun.
I hope it all goes very well for you. Please keep us updated.
Thanks, you guys. The doubled up BMBs were because both the Hopkins docs and the Seattle docs wanted to "have eyes on" the marrow themselves. Hopkins was particularly adamant about having its own because it was at the conclusion of a clinical trial and therefore of use to the drug company. Both also thought that actually going out to Seattle, having a procedure done out there, and consulting with them would help me get my foot in the door. Now if only I could, ya know, get into remission and go out there for good!!
You might really want to stay there for good. Seattle is such a neat city. If I move again, it will probably be to there. I love it.
I guess I can see the logic behind the two BMBs. Still, they could have sent the slides to the Hutch a day later or so and I don't think you really need to get your foot in the door there. Never heard of the place being overcrowded.
Keep us posted.
Oh, I absolutely loved it out there. If only my husband and I could get jobs there!! I'm praying that problems like that will become the ones we have to address... that would be a welcome change from, well, this. But seriously, the food, the atmosphere, the people, the attitudes, and yes, the coffee... LOVED it there.
I've been thinking about you and hoping your MEC + Sorafenib round was as painless as possible, and of course, remission-inducing...
I hope all is going as well as possible, and when you're up to it, I'd be interested to hear how you are doing. I tried to send a private message but couldn't due to a technical problem.
Thank you so much! I'll try to send you a message and see if that works. The MEC + Sorafenib was painless indeed -- I bucked the "Hopkins protocol" and went HOME right after my 5 days of chemo were finished! I took Sorafenib from days 4-10, then was instructed to discontinue it (they believe it's highly toxic and not beneficial when taken while completely neutropenic), then resumed it at Day 26 as soon as neutrophils began to reappear. I'm on Day 36 now, and have already had my bone marrow biopsy to find out whether this round was remission-inducing! On Monday, 7/30, we'll find out whether it was. If it was, I'll head out to Seattle for the transplant... we hope.
The only hiccup I've experienced is a week-long spike in my liver function numbers... they're starting to go back down, but my liver and kidneys have always been fine throughout this year of leukemia and treatments, so I went into a panic when the numbers went up. Other than that, I've been doing okay! Will keep you posted! I look forward to talking with you soon.
Just wanted to post an update... I've been out in Seattle for two weeks now doing the pre-transplant workup of tests, tests, and more tests. So far, the only drama has been that, despite my two rounds of MEC (April and June) and continued Sorafenib (July until now), my most recent bone marrow biopsy showed 0.39% blasts in the marrow (flow cytometry).
Despite my asking why on earth they didn't want to do anything to try to reduce that to ZERO before my transplant, they're not changing my pre-transplant protocol at all. If all goes well, I'll still be doing the targeted radiation study (http://www.seattlecca.org/clinical-trials/leukemia-NCT00988715.cfm)... and they hope that the radioisotope takes care of the minimal residual disease. I just HATE the statistic that folks going into transplant with minimal residual disease don't fare as well, because I already have several poor prognostic indicators (flt3+, Trisomy 8, relapsed, and refractory)!!! I don't need another!!!
The targeted radiation study wouldn't begin until September 24, so I just have to sit and hope that the disease doesn't flare over the next month, and that the Sorafenib keeps it away. Also, there are several points at which I could wash out of the targeted radiation study (e.g. if my bloodwork shows that I have certain antibodies), so that's not a guarantee. If I did wash out of it, I'd get some additional chemo and stronger TBI as my pre-transplant conditioning. NOT IDEAL.
Transplant is scheduled for October 9, if all goes as planned. Of course, we all know that "if all goes as planned" can amount to a hill of beans.
The thing I really, really wanted was the post-transplant AC220 trial (http://www.seattlecca.org/clinical-trials/leukemia-NCT01468467.cfm). The doctors here warn me, however, that I might not qualify for it following the transplant, for reasons none of us can control. The criteria include engraftment (over 1K neutrophils, over 50K platelets, and I forget the chimerism but it's on the link), morphologic remission at the Day +28 bone marrow biopsy (less than 5% blasts), and no significant GVH (must be below Grade 2).
So, yeah. That's how I'm doing. Hope you all are doing well!!! Best wishes to everyone!!
Sorry to hear about the blasts. Is that actually .39% or 39%? If it's 39% I'm surprised they're not working to get it lower but I'm not current on all the science. I'll keep you in my thoughts. Gotta love the tests, tests, and more tests. It's all for a reason but it does get to us after a while. Keep fighting like hell and keep us posted.
Yep, it's actually 0.39% -- less than 1%, wasn't even detected by the human pathologist looking at the surg path report -- but it showed up on the flow cytometry (I'm not super knowledgeable about how the flow cytometry is done, other than it is done by a computerized system and takes several more days to come back with results). I'm considered, as a result, to be in "morphologic remission," but if we're being honest with ourselves, the blasts -- albeit a tiny percentage -- are there. So I'm considered to be going into transplant with MRD: minimal residual disease. And I'm pretty bummed about it because, statistically, the transplants performed on patients with MRD don't last as well. But I know the refrain: I am not necessarily a statistic. And besides, hopefully I make it through these next two weeks of test dosing for the radioisotope trial and the pre-transplant protocol wipes out any blasts that may remain at the end of September.
Thanks so much for reading, take care, and I'll keep y'all posted!
Yep, it's actually 0.39%
See? That's going to get asked about. In the future you might want to go ahead and verify that you wrote it correctly.
However, that we're confused about that indicates that the 0.39 % isn't something that usually comes up as an issue.
Several key changes since last I wrote in.
I was able to go with the radioisotope trial (link provided in one of my posts above) which was an effort to ablate the bone marrow prior to the stem cell transplant.
Unfortunately, at my Day 28 post-transplant marrow, it was found that I still had minimal residual disease (MRD) remaining in the amount of 0.67% in the marrow, by flow cytometry. Yes, this is less than five percent, but it is bad because after a transplant, you DO NOT WANT ANY TRACES OF LEUKEMIA. NONE.
As outlined in previous posts, I'm being treated at the Fred Hutchinson Center - Seattle Cancer Care Alliance. I was referred here by Johns Hopkins, who refused to perform the transplant from an unrelated donor. The post-transplant plan here was to put me into the AC220 trial. The window for that trial is for people between 30 and 60 days out from their transplants, as long as they do not have major GVHD (I don't) and are in morphologic remission (i.e. fewer than 5% blasts) (I am).
Unfortunately, at my 30-day consultation, the providers at SCCA told a tall one about the status of the trial. They claimed that it had closed to new recruits, and was not expected to reopen until 2013 (i.e. my window would be long closed). Hopeless, and without any other recourse, having taken their word for the status of the trial, I agreed to begin a drug called Vidaza (also known as Azacytadine). It is NOT curative, and is intended to just keep the leukemia at bay until... well, for me, until nothing.
YESTERDAY, however (Day 53 for me), I decided to do a little sleuthing. It turns out that the AC220 trial was NOT closed, it IS accepting new patients, and I DO qualify. I informed my attending (they rotate, here -- we do not have one single attending who follows us from start to finish) of what I had found, and it wasn't pleasant, to say the least.
I'm waiting now to find out whether they're going to petition the drug company (Astellas) to see if I can join. If they refuse, I don't know what I'll do.
I'm young and otherwise healthy and not ready to die... It's really baffling to me as to why they wouldn't want to get me into the ONE potentially curative therapy for which I qualify.
Wish I had better news.
I'm sorry that you're dealing with this relapse. It's good that you did your own sleuthing on the drug. I hope you're able to get into the trial. I was on Vidaza prior to my transplant and it got me into remission. At the time I didn't know that it was an effort to prolong my life but it ended up being the chemo that did the trick. I hope you won't need it but if you do, hopefully you'll get the response that I did.
I know I replied to this, unless you have a similar post elsewhere. I was thinking they should have a number of options if this doesn't work. I specifically mentioned reducing or removing your immune suppression. I also mentioned I doubt the doc was trying to deceive you about the trial and that s/he probably had some bad information. There's no reason for the doc to lie about it.
Anyway, I'm sorry that seems to have disappeared. It was a detailed and very, VERY well thought-out response. Kinda sucks.
I am sorry you're having to go through this. But keep the faith. This ain't over by a long shot. They're going to get you through this.
I do have a similar post (at your suggestion!) elsewhere, and got your first response there. Don't worry; it didn't get lost.
They've phased out one of my immunosuppressants (mycofenilate mofetil) but i'm still on the other (Cyclosporine) and apparently will be for a while. They have such a paralyzing fear here of GVHD that it is hard to remind them of the potentially good GVL effect. Even so, GVL takes a few months to kick in.
And Kelly, even though I've discontinued the Vidaza after four days of taking it in hopes of getting into the AC220 trial, your post made me feel a LOT better about it, especially if I never do make it into AC220 (whether through trial or compassionate use appeal) and end up back on Vidaza again.
Only sucky thing about Vidaza is that it's a bridge therapy... sees people to transplant. But as for those of us who've already HAD the transplant... and aren't in morphologic relapse... there's just nothing out there. It's pretty unsettling. I have a huge number of people on this case (from some pharmaceutical lobbyists I know from back home, to my old docs from back at Hopkins, to the competent ones here at Hutch, to the FDA) so I am devoting 100% of my effort to getting AC220. I will keep y'all posted.
In the meantime, if you or anyone you know (or posts you have read) have any useful information about compassionate use appeals and how to be successful at them, please please pass them on!!
Thank you all for your support,
They have such a paralyzing fear here of GVHD that it is hard to remind them of the potentially good GVL effect. Even so, GVL takes a few months to kick in.
Fear of GVH? At the Hutch?!?! I don't know who you're taking to or if they've changed but they were always glad to see a little of it and they have a lot of research going on, or so I thought, on things like DLI and suppression withdraw to produce GVL. If they're afraid of a little GVH, that is not the Hutch I know and was treated at.
This whole discussion is making me wonder if there's something we're missing. Is there any reason they've mentioned to you that they're treating you as a "special case," if you will? Everything you're describing runs against the grain of the Hutch I went to.
I've read about a lot of folks on this forum who've had pretty rapid response to pulling suppression. Remember, the basic idea is that the aggressive cells attacking our body which causes GVH will also attack foreign cancer cells and gobble them up, too (GVL). It's really just making the cells do what comes naturally regarding cancer. The immune suppression slows them down from doing that job.
Again, I think something's missing here. Maybe I forgot it, I have chemo brain and don't always keep all my balls in the air. I'd just keep pressing them on it until I was convinced.
I'm sorry but I'm completely unschooled on compassionate use. Is there a particular med you're looking at?
Yep, fear of GVH. If I had a nickel for every time that this month's attending (by the by, I hate how the docs rotate and there is no specific doctor following a patient's case from start to finish), Dr. Petersdorf, has said "remember, MJax, GVHD can be life-threatening!!!!!" I'd be a very wealthy cancer patient.
I had a few bumps on my forearms (it looked like bumps one can get from shaving) and like two days of loose bowels (sorry for the TMI) and they put me on Budesonide and Beclomethazone (stomach-specific steroids) and the bowel issue normalized. Bumps went away as mysteriously and as quickly as they had appeared. That was enough to scare the bejeezus out of Dr. Petersdorf, who will not hear of me phasing off of my Cyclosporine.
Now, to her credit, she did phase me off the other immunosuppressant, Mycofenilate Mofetil (CellCept). But she and all the other doctors I've spoken to here say that there has not been enough time since my transplant to see a GVL effect against the leukemia itself. They say that takes a few months. I'm just shy of two.
I've learned quite a bit about compassionate use, and when I have more energy, I'll type a post here about it. If I'm successful in getting it, I'll type a new post dedicated to the topic in hopes that it will be helpful to others. Right now, I'm just waiting to hear back... and waiting SUCKS!
Waiting does suck. But we get used to it, don't we?
But she and all the other doctors I've spoken to here say that there has not been enough time since my transplant to see a GVL effect against the leukemia itself. They say that takes a few months.
Oh, okay, I think I see where we might have been talking at cross purposes on this. Yes, I imagine it would take a quite awhile for naturally occurring GVL to show up, especially if the patient is on immune suppression. I don't think it really takes that long when they induce it by withdrawing the suppression. That's where we've been talking right past each other. Glad that's cleared up, I was really getting confused.
If they've got you on B&B, they probably do think there's some GVH in there. They "knew" I had GVH but still did an EGD to biopsy and dx it before they started on the B&B. My gut GVH had gotten rooted just well enough that I wound up having to take Prednisone to fight it back. Then some other GVH showed up and I just stayed on it for years. But I was never dx'd with MRD. That's a big "but," unlike my butt.
I think they might be more worried about acute GVH at around 60 to 90 days post transplant. There is a lot to worry about acute GVH. That is the major hump that is most life threatening after transplant. Chronic GVH is not so fun either but it does not kill as often. I am now just over 3 years post transplant for AML FLT3 ITD. I had a sibling donor and the NPM1 favorable gene to mitigate my prognosis. I have a lot of annoying cGVHD but not life threatening yet.
At three years (didn't realize it had been that long, congrats) I don't think there's a realistic likelihood that you'd be able to develop any kind of life-threatening GVH. It took me about six years to get all recognizable GVH out of me but things that are going to be serious should happen much, much sooner.
It has been a hectic 5 months since I last wrote in with an update.
Astellas said NO on the compassionate use method of getting AC220. However, with the support of Hydrea and the Powers that Be, I moved back home (from Seattle to the East Coast) and started an AC220 trial that mandated that I wait until Day 100 post-transplant to begin. Got in just by the skin of my teeth... I was very sick.
Being home has been great, and I tried my best to separate my wonderful life of family, friends, etc., from all of the "what to do?!?!?!?!" drama. For the most part, I was successful. I didn't have much energy, and for reasons no one could identify, my lower legs and feet became so swollen and painful that at times I could barely walk. I even asked that my doctor (the Principal Investigator of the trial at this facility) to spare me the details of each bone marrow result, unless the results were so poor that remaining on the trial might no longer be prudent. I hoped to remain in the trial for years (when the trial ends, the drug company will not yank the drug from patients who show a consistently good response. How generous.). For the first 2-3 months (January through approximately March), my response to AC220 was so good that Astellas mandated a dose decrease (from 30mL to 20). Woohoo!
In late March, in addition to that pain and swelling and soreness in my lower calves and feet, and alongside that general lack of energy, I began to hurt all over. Then came a serious lack of mobility. By April 19, I was in my local ER for pain management (this turned into a few nights' hospital admission). I left the hospital on April 24 with a walker, and by April 28 needed a wheelchair to get around. Oh, and even standing and sitting caused severe, screaming pain.
I went to U Penn, where I'm enrolled in the AC220 trial, for the bone marrow biopsy mandated by the study. My doctor admitted me to the ER there for pain managment, and -- at my insistence -- to be observed so that we could figure out WTF was causing all this pain. The biopsy results DID show that things were changing, and not for the better. My doctor -- the one running the trial here!! -- now advises we do something else.
They immediately began checking the sample now for activation loop mutations -- if I had one, Crenolanib (closest available trial offering it is in Houston) would be the natural choice. But I don't have the D835 mutation, which is by far the most common mutation for people in my position. Tests continue, and it may turn out that I have another less common activation loop mutation, in which case he recommends I pursue Crenolanib. However, it may turn out that I have developed a resistance unrelated to flt3, in which case, well, nothing is really recommended...
I'll try to keep y'all posted!
I'm sorry things have gotten so messy for you. At least there are still some boxes to look under for some help. I'm rooting for you to find a lot of good stuff under them. Please do keep us updated. You could even have someone post for you when the fatigue and/or pain are too much.
I'm really sorry about this setback but continue to expect you to pull out of it and soar.
Sorry to have taken so long to get back on here with a response. A LOT has happened in the past six months, some good things, some bad. But I wanted to update everyone so that, hopefully, my story will help others.
I DID finally make it onto an AC220 trial in late January, 2013. It wasn't the trial that recruited people immediately post-transplant; instead, participants have to be at least 100 days out from a transplant (and/or awaiting transplant). I began on the 30mg dose of AC220 and we saw miraculous results very early on.
The results were so great that the drug company (Astellas and Ambit -- they are running the trial jointly) mandated that we decrease my dose to 20mg. Within days of doing so, I relapsed. This was late April.
As soon as we proved with a bone marrow biopsy that the leukemia was back, the company allowed for a dose increase back to 30mg. Again, we observed a fantastic response... though not AS fantastic as it originally had been. By this time, it's May.
I was then allowed to increase the dose to 60mg. Because this trial compares the 30mg dose to the 60mg dose, participants are not permitted to tweak doses between there. At 60mg, I developed a serious GI bleed after about 10 days.
Here, I should note that my counts never recovered once I started AC220. It inhibits leukemia, but for me, it is also inhibiting the development of neutrophils, red blood cells, and platelets. For the past six months, I have been receiving transfusions of red blood cells and platelets at least once per week. And for a couple of weeks before the GI bleed began, we noticed that my platelet transfusions were not making a difference at all. No bump, ever.
The GI bleed developed two weeks ago, and I nearly died. After several days in the ICU, I began retaining the red blood cells that were being transfused, but my body kept not responding to the platelets. At this point, my providers ran my HLA typing and another test called PRA (panel of reactive antibodies that shows whether a patient has developed antibodies to platelets) and these tests confirmed that I now require HLA-matched platelets in order for transfusions to actually help.
This brings us up to the past day or so. I've received three bags of HLA-matched platelets... the first two didn't yield a bump, but the third was miraculous. My platelets went from 2 (yes, 2K) to 57 from one unit alone. It will be hard to find matches all the time. Things are very dire now. And now, my hemoglobin is dropping, causing us to suspect that the GI bleed has either begun again or I'm bleeding internally elsewhere. There are no signs yet, so we wait.
Thank you all for your prayers, happy healing thoughts, positive vibes, and general support. It may take me a long time (months, even!) but as long as I'm alive, I'll eventually provide updates as I can. My family has instructions to provide an update when I die. I don't want anyone left in the dark, because I know I've used this forum to learn about trials and tactics that could work, and I know others must as well.
Until next time,
Thanks for being so open with us about the successes and trials you've been through. I'm so sorry you've had to experience all that but glad you're still able to get your gloves up for another round.
You know, if you could ask your family to let us know what's up when you're not able to, we'd be able to focus thoughts and prayers a little better. Just a thought.
Hang in there and know there are people here rooting for you and anxious to learn about and from you.
Hi, All. This is MJax's husband; she asked me to provide an update should it be necessary. I am very sad to tell you that MJax passed away at the beginning of October. As she wrote in July, she was no longer responding to platelets, matched or otherwise, so eventually the platelet transfusions were discontinued. Blood transfusions became more frequent, but with no platelets the bleeding was uncontrolled. Her counts never recovered while on the AC-220, and they ran out of other ideas/options. She grew progressively weaker, but fortunately she was able to be at home at the end.
Thanks to all of you for the support you provided to her throughout her time on the boards. She was truly a remarkable woman, and I was lucky to have had her in my life. I wish you and your families strength, courage, and all the best as you continue to face this disease. My prayers are with you.
My deepest sympathy to you! She seemed to be so fearless and intelligent. I have followed the story she presented very closely because her diagnosis was similar to my husbands and I was hoping for a better outcome. AML is such a terrible disease. I also want to thank you for the update. MJax will not be forgotten. -Kerry