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. However, at my six-month biopsy on April 16, 2012, I was found to be only 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.
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 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 should add that I spoke on the phone with an oncologist at one comparable hospital, and emailed with two oncologists at a second comparable hospital, and none have concurred that the DLI is the best (or even a good) route. I understand that the hospital where I am currently being treated is supposed to be one of the best, but the opinions I've obtained are at odds with the opinions of the team treating me.
So I am posting in hopes of finding out what other survivors in similar situations have done.
Thank you so much for reading!! Much love.
First thing I'd recommend is that you find the transplantation forum and post there. Not that many folks here have been through transplant and you'll find a lot more input there.
Would you mind naming the center you're at? To decide on a haplo without even consulting the registry sounds pretty strange. I guess one of the top centers would be the first to know and switch protocols if haplos worked better with your particular form of the disease and your cytogenics. It does seem strange to go with the 70 year-old mother but I would assume they have their reasons.
That said, without a better understanding of what the docs are thinking, I'd be reticent to try to advise you. To reach a chimerism of 80% is good but you would want to get higher over time. If you just had your myeloblative haplo in October (?) I can understand why they might prefer to go with a DLI over a second transplant. It would be kind of soon to put you back through the conditioning protocol.
I think I'd want a second opinion from another top provider but with active AML, there's not always time. Still, right now your job is to get back into remission. That should give you time to set up some other consultations, at least by phone.
DLIs do work. Since your mom's cells didn't produce GVH and it sounds like they want you to have some, I'd want to know why they think this procedure would improve things, first.
I don't know. I wish I had some better insights for you. Maybe you'll find them on the transplant forum.
Thanks very much for your feedback!
I'll definitely search out the BMT forum for some additional input.
A quick note regarding the chimerism... it had been 100% donor marrow for 6 months, and then dropped to 80% with the relapse, so it certainly won't be climbing back up on its own. The question is whether to opt for a DLI or a mini BMT from another donor entirely...
I am really hopeful about getting into a trial in Seattle. My doctors actually prefer it over their pet favorite, the DLI. It would combine a mini BMT with FLT3 suppressor AC220. Fabulous. Assuming a donor works out. But if I do not get into that trial, the original question will bound right back.
Will keep y'all posted!
I had my transplant in Seattle. I guess you're talking about Fred Hutchinson and SCCA. They are the best there is IMO. If they're working on a trial, well, they don't always work...they're human. But they have some incredible researchers going on and they are really detailed.
All I'm saying is, if you get into the trial, you'll be treated by top-notch professionals in every aspect.
It does seem like it might be a bit soon for you to undergo the conditioning for another transplant using a different donor, and we've had some folks here who have had a DLI turn things around for them. I would want to know why they are not considering Nexavar (sorafenib) in your case. I hate to say it, but it almost sounds as if they are more interested in their trials than in your welfare. Remember that they work for you. Push for whatever is going to give you the best chance.
Please keep us posted.
Thanks so much for your response. At this point (relapsed and about to undergo chemo) Sorafenib/Nexavar wouldn't be appropriate, as it would quiet down the very thing the chemo is supposed to kill. But I'm less worried that they're prioritizing their trials, and more worried that they've forgotten about me in general, since there was a post-transplant trial that used Sorafenib and they didn't even ask me about it. I found out about it from a fellow patient, and at that point it was too late to join.
As for the conditioning regimen, it would be a very different one entirely... We humans can withstand only one myeloablative prep regimen at all, I'm told, so a second BMT would be a "mini".
It's great to hear that DLIs have helped some folks on here.
It looks like I may transfer to Seattle after this chemo (which hopefully will put me into remission). In Seattle, they're running a trial that combines AC220 with mini-BMT from unrelated donor.
If for some reason I don't make it into that trial, I guess I'll stay where I am, give the DLI a shot, and beg for Sorafenib.
I'll keep y'all posted!! Thank you again!
From your description of the proposed plan, it sounds like your docs might be intending to use Plerixafor to drive the blasts out of the marrow. There's an article on it at http://universitycity.patch.com/articles/drug-makes-leukemia-more-vulnerable-to-chemo
There's another new drug called Vorinostat that appears to have promise (85 percent remission rate). See the article at http://www.mdanderson.org/newsroom/news-releases/2011/aml-patients-have-high-response-rate-with-vorinostat-added-to-treatment.html
Nexavar helped me get my peripheral blasts down to near zero (from 20) in about a month's time. I had it with chemo and have been taking it at home for the past month. Had a biopsy ten days ago and results are still pending. I'm also pending the results of a PCR test for FLT3. Because of those uncertainties, it would be premature for me to start cheerleading for Nexavar at this time. There's a Nexavar thread here on the LLS AML page...I'll be likely to post the results there when they come in.
Stay involved in your care, keep a smile on your face and keep fighting.
Thank you so much for your response!
The drug they're testing is not the one you linked to, but similar... It doesn't have a name yet, but it targets the CXCR4 geneand apparently I'll be the 12th human on which it has been used... so that's cool (HA, not really). Vorinostat will be part of the MEC chemo regimen that targets the study drug.
I'll beg for Sorafenib following whatever treatment we go for after this chemo (DLI or mini BMT). Looking forward to hearing about your pending results, and praying that they are good.
One quick comment to pass along. I had the MEC chemo regimen in my 3rd induction. Apparently it's an old standby, as I've Googled it and found it's been around for at least 20 years. By itself, it was just as ineffective as the first two inductions with cytarabine and idarubicin/donarubicin had been. My blast counts were still in the 10-20% range. It wasn't until they added Sorafenib to the (high-dose) cytarabine and idarubicin in the 4th induction that we saw positive results.
Interesting!! If you are willing to share where you're being treated, would you please let me know where they are doing that? I am at Hopkins, where they insist that Sorafenib shouldn't be combined with chemo (they use it afterward, to maintain remission) on the logic that it would quiet down the blasts, making them less receptive to chemo. I am intriigued by the stories of Sorafenib's uses and effectiveness on these boards. The Hopkins view of Sorafenib seems quite negative and I'm having trouble understanding why.
Thanks for letting me know!
I'm being treated at the Salt Lake City VA, whose medical staff also work at the University of Utah Medical Center and the Huntsman Cancer Center. They initially gave me the Sorafenib for 7 days, in conjunction with 3+3 of the IV drugs, based on what they read from the MD Anderson clinical trials.
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.
Well... I'm feeling like I finally know what a "Hail Mary pass" is. I researched a hospice in my area last week, and doing so actually brought me a bit of comfort. I am still really curious as to what the dying experience is like in the leukemia context -- I hesitate to search for details on it, though, as the superstitious person in me fears that that will solidify a negative outcome. I was pretty upbeat throughout my induction and transplant, and even in the first course of treatment for my relapse, but I've fallen off somewhat.
I'm much more interested in the dying experience of a 99 year-old man having a heart attack while having sex with a 19 year-old girl (providing my wife pre-deceases me, of course). I'm trying to qualify for that one.
I know it's got to be a tough place to be in. Try to keep your focus and stay determined as much as you can.
I could tell you were being treated at Hopkins, my husband has had most of his treatment there as well (AML FLT3+ mid twenties also) and so much of what you were describing resonates with our issues. You are correct in that they view sorafenib negatively and I don't know why either, for my husband it was a miracle drug and saved his life. He went out to Seattle for his transplant since he could not get into remission at Hopkins and they have a lot of novel trials in Seattle (I could write a book about my love of the Hutch). He did relapse shy of day 100 and the Hutch folks applied for sorafenib for him as compassionate use three years ago and paired that with a DLI (he didn't have any additional chemo) and that put him into remission. Seattle told him to take the drug forever if he could tolerate it. He had an inpatient stinit last summer at Hopkins and one of the inpatient docs was baffled and almost rude as to why he would still be on it if he had chronic gVH, said there is no need, and took him off of it. I know Seattle does TONS of research and is on the forefront of therapies and I trust their opinions wholeheartedly. Now I see the signs you see along the halls, that Hopkins is #1 in the country, and I feel your frustration on their decisions at times. I don't get why they seem to disregard sorafenib, they seem to have a different agenda with this medication than other places. It sounds like you've been doing you research and making the right contacts, go with your gut on this one and be persistent. It is easy to feel forgotten and perhaps get forgotten with as big as that hospital is.
Thank you so much for your kind, thoughtful response. It is a relief to know that others have made the Hopkins-to-Seattle jump and have met with success. Although the prospect of heading out there is extremely daunting, I'm comforted by your words and your confidence in their opinions.
What is "compassionate use"? I haven't come across that term and am curious, especially since - being at Hopkins at the moment - it's impossible to learn anything from the team here about Sorafenib. Did your husband experience any negative effects from being taken off Sorafenib?
I assume you're back at Hopkins from time to time because the location is more convenient for you... that's how it will be for us, following (hopefully!) my time out in Seattle. If this is the case, has your experience with Hopkins for follow-up appointments after treatment in Seattle been okay?
I've learned in the past two days that I will definitely be able to transfer out to Seattle for the trial I described IF this induction chemo gets me into remission. So I'm hoping it does! I would be thrilled to have the opportunity to benefit from the expertise out there.
Hey, one the fellows I had assigned to me at the Hutch was fro Hopkins. Just feeling left out.
Compassionate use generally means that the med is sent to the patient who doesn't qualify for a trial because nothing else is working. That probably needs some fine tuning but should get you by until someone can offer a better explanation.
Congrats on the trial. Now kick those damned blasts out of your system and get on with things.
Thanks for the explanation re: compassionate use.
I will probably be off of the boards for a few days while I try to muster some positive energy and let this induction round do its thing. In the meantime, I hope that when I return to the boards, there will be some (or at least one) story of ANYONE who was "cured" by a second BMT after relapsing in the wake of a failed first BMT. The Hutch wants to try it, and I want to go, but I still haven't come across anyone for whom a second BMT was the golden ticket.
Take care and I'll keep y'all posted!
There have been people cured by a second transplant. The thing to be aware of is that not many people have to go through a second and therefore there might not be anyone posting at the moment who has. There are so many people that with my chemo brain, I really can't remember what everyone had and where they are in their recovery.
But people have been helped by the second transplant. This seems to be something that does happen a lot with related donors, though you're the first I can think of from a haplo. Don't worry about that. Get yourself determined to kick this thing's butt and go from there.
MJax, i am so sorry you are going through this, any of it. My son was diagnosed with aml at 18, relapsed at 20 and had a double u cord transplant. It is such a difficult road, physically and psychologically.
Just to elaborate on what tex said, and maybe a little different perspective, this is a very difficult forum for people to stay attached to. Most survivors or family members, after such difficult journeys, move on with their lives, realizing aml or whatever disease that has brought them to transplant has taken enough from them.
With that being said, second transplants certainly aren't as common but there are quite a few here that i have seen over my five years that have endured 2nd transplants.(PJ, Anne, Sandra's Hamish to name a few) Tex, i forgot the one young woman, her mother occasionally posted, relapsed about the same time as Hamish and had a 2nd transplant. Was it marie?? Anyways, they were later relapses and all had 2nd transplants and we do hear from them time to time.
We have had a few that were early relapses and had 2nd transplants, Artmark, if i remember correctly, comes to my mind. He has also posted a while back, and Cathy's husband Owen (she posted under name secondtimearound) was FLT3 positive, and on sorafenib, didnt he have a second??.
So there are folks. Your journey will be your journey but you are young, strong, determined, and you can do this. And you have a wonderful hospital in the hutch that believes you can.
Rest your mind, let the chemo do its job, shouting a little prayer up there for a little help along the way. (((Hugs)))
I see Diane (MW) checked in and she remembered all the double-transplant folks I remembered. peejay, Secondtimeround, Reese (daughter is Marie), Chocccrackles (her son Hamish was the patient). As far as I know, all are doing well. We haven't heard from Reese in a long time, and it's been awhile since Cathy (Secondtimeround) checked in. Here's a link to her thread, which you will probably find relevant since Owen also had the FLT3+ issue.
You can search the other threads using the user name, assuming you have the energy (I am hoping you have the time because things are going boringly).
At any rate, it's been done and we have folks around here who have managed it. Stay determined to kick this thing's butt.
Hi WBF and WarriorMama!
Thank you for the reading references!! While all of our situations are nuanced and different, it is so helpful to learn of similarities where they exist and positive experiences that others have had. I really appreciate the time you took to pull some for me.
First time posting here. I sound like I am in a very similar position to you. I am 27, had my BMT about 5 months ago and am also flt3+ and relapsed. My transplant was from my brother. I am being treated at City of Hope and after discovery of relapse started Sorafenib and 3 sessions of outpatient. chemo (decitabine). Just finishing my last session right now. After the first round of decitabine and sorafenib I am in remission again and plan on having a second transplant from an unrelated donor in a month or so. Also curious about second transplants because they don't seem that common. I've met a couple patients in the clinic who have had them. Anyways, not sure how helpful this is but let me know if you want to talk.
Let me start by wishing you the best. Yes, it's a tough fix we got ourselves into, one in which science is almost the 'luck' part of the deal.
Secondly, thank you for letting me know about the decitabine and sorafenib. Was that part of a clinical trial, or just a regular therapy option? I'm curious because the clinical trial options available to me are slim and might involve negotiating red tape concerning authorizations and protocols. I don't have a lot of time to slog through the paperwork jungles. (That's one area where I've always felt the sword is mightier than the pen.)
Let me close by again wishing you the best. Keep your spirits up, and remain engaged in your treatment decisions. There's a way through this, and hopefully the good people here in the LLS community will help us find it.
Thanks Bob! I am not participating in a clinical trial, I guess this is "regular" therapy. Although, don't think too many other patients there are undergoing the same protocol. I do know its kind of considered an off label usage of sorafenib and I was only able to get the medicine through a specialty pharmacy. Thanks again for yor support.
I wanted to share with you my daughter's, Michelle, journey thus far. She was diagnosed in March 2011 with AML FLT3. I'm going to skip the info on all of the rounds of chemo. She had her BMT in Sept. 2011. My younger daughter and I were a half match but they chose my younger daughter because her and Michelle have the same blood type (different from mine). They believe she got a small amount of GVHD but they weren't really sure. Afterwards they believe she didn't because after the transplant they did a bone marrow biopsy and she was 100% DNA of her sister but here's the kicker, the Leukemia blasts came back after 6 months. She had to go back into the hospital for a 5 day round of chemo. The also performed a Lymphocyte Infusion (also taken from my younger daughter) in April. After her discharge this time they prescribed Michelle the oral chemo, Sorafenib. She was told she would be on this for a few years. This past weekend we had Michelle's one year birthday (since her BMT). It was great! So we take it one day at time and always, always pray.
You're right: it does sound like we're in very similar situations, and I'd love to talk with you! I'll send you a message with my e-mail address, etc.
I'm so glad to hear that your post-relapse protocol was successful! I have never done outpatient chemo -- have you been feeling okay throughout your rounds of it?
Will City of Hope be doing your transplant as well? Seattle (Fred Hutchinson Center, Seattle Cancer Care Alliance) will be doing mine... if I get to remission, that is! My bone marrow biopsy today will let me know!
From your timeline, it sounds like they have a donor lined up, which is fantastic! Seattle's search is in progress for me, and to my understanding, there are several potentials. Fingers crossed!
Hope you are feeling well and staying confident. Talk to you soon!
You may want to check out a post in the Chronic Myeloid Leukemia board about Genome Research about the flt3 gene. Very Interesting. They used the drug Sunitinib which targets the flt3 gene. Here is the link I copied from the post.
I found the doctor's email and phone # if you search the University he is with.
Thanks for your response! One of my doctors here at Hopkins, Mark Levis, was influential in testing Sunitinib. Fortunately for folks with CML and ALL (like the man in the article, who has ALL), the flt3 gene in ALL responds quite well to Sunitinib. Unfortunately for AML folks like me, the flt3 gene in AML responds poorly to Sunitinib, and responds much better to Sorafenib, and best of all to AC220.
But the process they went through to target the flt3 gene for him, and to treat it, is remarkable and can help us all!!
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!!
Just to be sure, did you mean to type that the blasts were at 39%? I know they wouldn't have been concerned about 0.39% (0.0039) when I was there. They just wanted me under the 5%. And, as I was at 30% when I reported, they went ahead and put me through another induction.
I washed out of the isotope trial before I began because I was too old (over 40 at the time). I had a room next to the hot rooms and that was a whole different world in there for those folks. I'm guessing they did well if the Hutch is still working with it. So, good luck with that.
If I understood what they're trying to do with the isotopes and remember correctly now, chasing down extra leukemic cells might not be necessary because, as I remember it, the isotopes are supposed to attract something to attack every cell. Then again, the doc I talked with had a heavy accent and I'm hard of hearing. He might've been reciting a salad recipe for all I know.
Thanks for checking in. I hope everything goes the way you want it to. And do keep us informed.
Yep, it's actually 0.39% -- less than 1%, wasn't even detected by the human pathologist looking at the slide -- 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!
Or rather, my husband will be the one keeping y'all posted... I can't seem to keep from wandering into forums that aren't very good for my confidence... I tend to feel very, very down when I do much (okay, any) reading about strong, fighting folks who didn't make it.
I didn't come onto these forums until six months after my SCT. I was concerned I'd have the same reaction as you and thirty success stories would be challenged by one that didn't work out so well. I stayed off the 'net until I was ready. So, I'll look forward to meeting your husband and getting to know him as we cheer you on.
I don't know what they've found out in the past eight years but when I went through my relapse/SCT, they told me that the stats were better if they could get my blasts under 5%. They did that and here I am eight years later. I can't believe that 0.39% is a concern for them. The conditioning chemo is supposed to kill off anything that's left. And, again, they just wanted me <5%.
I know we can find reasons to be worried. I don't think this is a major concern for you. Your new immune system won't have much -- if anything at all -- to kill off. And after conditioning, I'll bet you're at 0.
If your docs are focusing on this, they're just playing CYA so ya'll can't sue. But you can, if there's a reason.
I know it's difficult but try to just blow that off.
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've got to believe the doc had bad information about the trial. Not only are the folks there top notch, but there's absolutely nothing for anyone to gain by lying to you about it. Not like the company is paying doc to keep patients away from the trial.
I hope you get in. If not, there's got to be a way to try to stare this sucker down, including inducing GVH. I'm surprised they haven't reduced your immune suppression, if not pull you off of it all together. There are usually a number of ways to go after MRD. It might be a weird situation where you don't qualify for any of those treatments but I've not heard of that before.
You might ask your doc to comment on what I've just written. If I'm off base, I do apologize in advance.
Bad information indeed. With the Hutch being only one of four centers with this trial (AC220, post-transplant, 30-60 days out) open, I cannot adequately express my anger at the fact that they managed not to know the status of the trial in time for me to get into it. That trial is the whole reason I came out here from the other side of the country!!
So, they told me it was closed. As a result, to deal with the MRD, I ended up starting a chemo called Vidaza, but that felt so stupid because Vidaza is used primarily on (1) old people and (2) people on a "bridge" to another, more effective, treatment... such as a transplant. It isn't known for bringing people into remission and then making them stay there forever. I only did four days of that, though, because THEN...
I found out an insane thing. The AC220 post-transplant trial was NOT shut down after all!!!!! The doctors here made a horrible mistake. They told me it was closed, when in fact it was not. When I found out that the trial was open, I was informed that the freaking VIDAZA made me ineligible for it!!! Vidaza that I never EVER would have taken if I had known!!!!!!! See, I'm at Day 56 post-transplant now. I only have until Day 60 before the trial window closes. To be eligible for the trial, one cannot have had chemo within 21 days of starting the trial. In short, I'm screwed.
The doctors are now trying to get AC220 for me through compassionate use. We'll see how that goes. Otherwise, I really have no options left. I'll keep you posted!!
And of course, I'll continue to press on getting my immunosuppressants phased off... But as we discussed in the other forum, the doctors here have phased me off one (mycofenilate mofetil/CellCept) and are unwilling to pull me off the other (Cyclosporine) at this time. I currently have no signs of GVHD. I am hoping for an attending physician to come on rotation in December who will be amenable to phasing me off the other immunosuppressant in order to stimulate a graft-versus-leukemia effect. However, the doctors with whom I've spoken here say that it takes a few months to see GVL.
This certainly isn't the Hutch I knew. I'm so very sorry and as I write that I realize how absolutely useless it is to say it. It doesn't fix a damned thing that I'm sorry. And this is the type of situation that needs some action.
I hope and pray you get compassionate use. I think Kelly on the transplant forum should have some guidance for you. He also went to the Hutch and he relapsed as he neared hi five year anniversary. They were going to bring him back to Seattle and do a DLI on him but they pulled his suppression beforehand or something. He never wound up needing the DLI.
I'm pretty sure he's already responded to your post over there but can't remember what he had to say. He should have better insight into the Hutch's typical view on GVL.
Check out: http://clinicaltrials.gov/ct2/show/NCT01349049?term=Plexxikon&rank=3 as a possible alternative to the Astellas trial.
This is actually really interesting. One of my doctors is listed as a Principal Investigator at his center for it... So even though there are some hiccups (must be off all immunosuppression, etc.) I will definitely be asking about this today. Thank you so much for posting this!
It's a report of a drug study for people who are FLT3+. I'm not sure how it would apply to someone who's had a transplant though, but it's something that's out there. Per the report, the drug works much better on those who are FLT3+ than on those who aren't. I'm also not sure whether it would be beneficial to someone with such MRD as you. I hope the MDs at the Hutch can manage to get you the original drug through compassionate use.
I, too, was a bit confused about your flow-cytometry report. Remission is generally considered to be when the blasts in the marrow are < 5%. I surprised that they haven't lowered your immune-supressant drugs to let GVL take effect. Consider all the people who are now getting reduced-intensity conditioning pre-transplant: most of them must have MRD, because they haven't done the radiation, and the chemo isn't of as high intensity as the normal dosage. I guess I'm just confused.
Thanks so much for the link. Yep, Quizartinib... a/k/a/ AC220... That's what I want so badly. It's SO PROMISING for flt3 folks. My MRD is still flt3+... stupid flt3. My AML always did have that, so I wasn't terribly surprised when it came back through after Transplants #1 and #2.
Regarding the immunosuppression, they have fully phased out one of my two immunosuppressants (it was called Mycophenilate Mofetil, MMF, or CellCept) and now they are in the process of phasing out the other (Cyclosporine, aka GenGraf). Because these have to be phased out slowly, my last Cyclosporine dose will be January 18 -- aka Day 100 for me. Hope that clears things up...
Yes, morphologic remission is considered to be when the blasts are lower than 5%. But when there are any blasts at all, that's Minimal Residual Disease, and those blasts can and do multiply. As of today, mine have gotten into my peripheral blood (even though they were only 1.9% in the marrow, and none in the peripheral blood, 3 weeks ago). This disease moves QUICKLY.
As for the folks getting reduced-intensity conditioning pre-transplant, my docs tell me the transplant itself usually knocks out any MRD. It didn't, in my case, and now it's growing.
Options on the table (in addition to phasing out immunosuppression) include AC220 if they can get it through compassionate use, the clinical trial that Bichette linked above, and DLI. Or a combination of these things.
Will know more after today's biopsy, but I probably won't write back in until there's a plan in place. I'm getting stressed out.
I'm getting stressed out.
Let me ask you a question you might find offensive (i hope not).
If it turns out you only have three months to live, do you want to live them stressed out, with negative emotions?
I was certainly unsuccessful a lot of the time but I did my very best to just relax and figure things are going to work out. Turns out they did. And I'm still glad for every second I spent not worrying about it.
Like I said, I didn't always pull it off but I really tried.
Remission is generally considered to be when the blasts in the marrow are < 5%.
And CR is when we hit <5% and our counts have returned to normal, Or so I've been told. Wth, I'm not a doc.
This whole thing about morphologic remission is a concept I've just seen a couple of times and only recently. I'm thinking it's something they've just figured out or just figured out the importance of. Like many changes I've seen over the years, it will filter through the field, be looked at some more and ultimately disappear or become a permanent fixture...at least until the next new thing comes along.
After just reading MJax's recent latest replies, maybe the whole thing is just a word I haven't noticed before. MRD has to be a concern because they're the seeds of relapse.
When the blasts are under 5%, the disease isn't considered active, thus, "remission." But they still want to get it all gone or the disease might well come back. The thing I don't understand is why they're not doing more to reduce his cyclosporine because GVH is required for GVL. They need to get his immune system cranked up so it will gobble up the remaining disease. At least, that has been the common wisdom for as long as I've been in the BMT/SCT community. It's why I'm puzzled by the response of the doctors at the Hutch who were reticent to put me back on immune suppression, even when my GVH was kicking back up at the five-year mark.
By the way, I've been in bed, actual bed, with a bad cold and fever the past few days. I think I'm writing coherently but, if I'm not, that might be the reason. That's assuming my writing is usually coherent, of course.
Re: the morphologic remission and MRD discussion, I'll write exactly what a doctor at the Hutch told me:
Re: the question on how I'd like to live my life, regardless of whether it's a day, a year, or 100 years:
Tex, I hope you've recovered from your cold and are feeling much better!!
Okay, so I've either been completely unobservant of the word "morphological," have had a rather extended chemo brain moment of late or it's a term not used around me until recently. Any of these are quite possible. When I was first told I was in remission, that's what they were talking about.
When I was first dx'd the visual count was 20% blasts but the Flow showed 43% or 48% (one of those curvy numbers). Which explains why they were using MDS and AML interchangeably. Amazing how much detail I used to know that I simply can't rely on knowing anymore.
As for the question, we can never get it out of our head completely and I'd never suggest we should. It's one of the tricks I learned to distract myself because I simply couldn't live with the stress 24/7 and had to find a way out of it sometimes.
I remain troubled by the lack of accurate information you've received. That would be bad anywhere. At the Hutch, it remains a huge problem and I'm still astounded by it.
You're here today. That gives you a more than fighting chance at tomorrow. String enough of those together and you're post-AML. So kick ass.
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,
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 ideas/options. She grew progressively weaker, but fortunately 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 famillies strength, courage, and all the best as you continue to face this disease. My prayers are with you.
Thank you and condolences. I am sorry to learn how the story of her disease concluded. We never know folks well on these forums but she was a true trooper and, I think, a role model in many ways.
My only regret is somehow we all missed her last post and she didn't have a response. I am so sorry for that. These forums have hiccoughs sometimes but nor usually this poorly timed. I hope she knew we cared for her all the way through and we didn't intentionally abandon her when things got tough. That's when we usually try to be there the most.
Thank you again for letting us know. I hate this disease and the destruction it wreaks. I pray for strength, comfort and peace for you and your family.
It's with sorrow that I pass along my condolences to you on the death of your wife.
I closely followed her posts from last year from when she was at Hopkins and pursued treatment at the Hutch. I was going through the heaviest part of my treatments for AML and FLT3. I thought I had done quite a bit of research about our disease and possible treatments. Your wife went much further and explained the latest diagnostics and trials to us. I especially admired her courage and outlook, as in her own words, she was on "the quest to do my best".