Moving towards BMT

[kjraimondi]

Hello all,

After about four months it looks my docs are moving me towards a BMT. I have had a response to the first round of horse ATG but not what they consider a "significant" response. The latest study's are showing that doing a BMT within the first year post diagnoses heightens the success rate. Patients without a significant reaction to Horse ATG are not faring as well on the second round of ATG and it just furthers the time before they end up needing a transplant and they are at risk for developing MDS.

Many of you are far more educated than me. Please take a look at this recent study and share your thoughts.

https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B62tiAapLHJVMmUwOTJlYWUtNGVhZC00YTkxLTlmZTItZjhhMTU5MzY5N DY3&hl=en_US

I am looking for the best long-term treatment and this may be the best chance I have at having a successful BMT but I want to hear your thoughts. They have started the donor match and they believe they will have no problem finding a 10/10 match. If that changes my opinion will most likely change as well...

Thanks again and... Merry Christmas!!

Ken

[Tonilee]

This is my first time on this forum. My husband was diagnosed with severe aplastic anemia at age 39- and it has been a life changing experience. Although it was incredibly unfortunate to be diagnosed with this disease, we were so lucky that his brother was a bone marrow match. After intense treatment to get his body "ready" for the transplant, I must tell you that it was a success! However, I would be lying to you if I told you if I told you that he feels great now. He has nerve damage and joint pain from the chemo; however, he is happy to be with us and our two boys (who were 4 and 2 at the time). Every day is a new day and a gift. Keep a positive outlook and ask people for prayers and support (which you may have been already). God Bless You.

[Greg H]

Hey Ken!

This is a really good article -- and it makes a pretty convincing case for the route you seem to be headed out on.

If I can summarize the argument of the authors, as I read it, they say: We're getting a lot better at BMT, just look at the data. Plenty of studies show early BMT is more successful than late BMT, when infections and other complications get in the way. And besides, living life immunosuppressed has its downsides, too, particularly if your response to the IST is not all that hot.

Most of the data they actually share has to do with point #1 of the argument: "We're getting a lot better at BMT." Their slide form National Marrow Donor Program illustrates this well: there's a much nicer survival curve for 2003-2006 vs transplants done back in the 90s.

I was able to find the same graph with even more current data on the NMDP website. It looks like this:

[IMG]
saa_adult_over_time_large by hankins.greg, on Flickr[/IMG]

What I thought was interesting about this is that the 2007-2009 curve is about the same as the 2004-2006 curve. In other words, we've made some progress in survival after BMT for AA since the 1990s, but we haven't improved much in the last five years. And, really, the newer curves are only about ten points better than the 1990-2003 data.

Reading the paper closely, the authors seem to lay most of the improvement in the 2000s vs the 1990s to the move away from harsh conditioning regimens, particularly total body irradiation (TBI) and toward regimens that instead rely on cyclophosphamide (CY) and fludarabine with various combinations of other immunosuppressants (ATG, Campath, etc.)

So, the old idea of using TBI and harsh chemo as a conditioning regimen was killing 60-65% of patients in the first twelve months. As the new regimens using fludarabine came into vogue, the year-one mortality has dropped to 30%.

So, the first conclusion I take away from this is that, if you're doing an old-school TBI-CY transplant, all the nice things the authors say about improved survival goes out the window. They are encouraging not just ANY early transplant, but early transplant using a specific type of conditioning regimen.

Beyond that, if you consult Table 2 on page 1484 (I can't make a version of this table to insert here, but it's in the article Ken originally linked to), it seems some drug combinations and/or some docs can produce very different results. Overall survival is pretty good in most of these. Otherwise, there's a lot in this table to ponder. Bacigalupo, using Flu/CY/ATG has 18% graft failure (pretty high!) but little GVHD. Srinivasan, using Flu/CY/ATG has no graft failure, but lots of GVHD. The difference appears to be that Srinivasan used peripheral blood stem cells, while the Bacigalupo study used marrow.

I'm not educated enough about these different techniques to say much more than that all this would make me, if I were about to have a BMT, very interested in a detailed explanation of exactly what kind of conditioning and what kind of cells we would be using, why the docs think that's best, and what kind of data they have on engraftment, aGVHD, cGVHD, transplant related mortality, and overall survival.

My guess is the reason we haven't seen improvement in the curve in the past five years is that the transplant community is still figuring out the best combination of drugs to use.

I hope that's useful. I learned a lot trying to understand the article.

Take care -- and good luck!

Greg

[Marlene]

Good job on summarizing the article Greg. The article I posted earlier in News and Events speaks to the blood stem cells vs bone marrow cell for use in transplants.

They found bone marrow cells have higher graft failure but better GVHD outcome while the peripheral blood cell have a better graft rate but with a higher rate of GVHD.

Hopkins has been successful using HiCy for two days right after the transplant to prevent GVHD. So if you combine the above with a reduced conditioning regimes, you may end up with an optimal approach.

Reduced conditioning + blood stem cells for better engraftment, followed by two days of HiCy to minimize GVHD. It certainly is more complicated these days to figure out what path to take.

[kjraimondi]

Thanks Greg! Excellent break down. I know my BMT doc had ruled out TBI...He said up front that that was killing patients in the past. Once a match is found and we have to decide 100% then I will discuss with him what you shared. I appreciate you very much!

Ken

[Greg H]

Hey Ken!

It was fun (and educational) trying to understand the article.

Marlene, I saw that article you posted. Also very interesting. I know that sometimes, for MDS as opposed to AA, the docs want to do reduced intensity and use peripheral blood in order to get a little GVHD for the graft versus leukemia effect.

I think that post-transplant HiCY is just what Karen (mausmish) had at Hopkins.

And I do think you are right that it's much more complicated, as the docs try to get just the right mix of drugs.

Take care!

Greg

[mausmish]

I did have post transplant HiCY at Johns Hopkins but had full myeloablative conditioning (Busulfan and Fludarabine) and bone marrow rather than stem cells. Hopkins uses marrow to reduce incidence of GvHD. I was not considered for reduced intensity conditioning because of the severity of my MDS and my otherwise good health. They don't do TBI for MDS At Hopkins anymore.