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