[This post is a little unusual in that it's really long. But I've noticed a lot of younger MDSers hanging around here, and I think the theory of the disease and the possible treatments for younger patients that I describe here is important info that gets short shrift in a lot of the usual MDS handbooks you pick up at the oncologist's office. I wrote this for my family, so it's a little elementary for you guys. Hope it's useful.
— Greg]
To hear the guys at NIH tell it, there's a war in my bone marrow.
NIH is the National Institutes of Health, a collection of incredibly smart health care folks who do their investigating mostly at a big campus in Bethesda, MD. The hematology folks there have been methodically working through a theory that some types of MDS begin with an immune reaction gone awry inside the bone marrow. Their research has ranged from test tube work to clinical trials, and understanding the details gets way beyond my college freshman biology and chemistry. But the basics aren't all that tough.
Stem cells with some chromosomal abnormalities -- particularly Trisomy 8 (three copies of chromosome 8, instead of the usual two) -- have on their surfaces proteins that provoke an immune reaction. The immune system sees these proteins as the uniforms of an invading force, and starts multiplying certain T-cell lymphocytes to do battle with the intruders. I happen to have the Trisomy 8 abnormality in about half of my stem cells.
So now we have my T-cells attacking my own Trisomy 8 stem cells. Unfortunately, the Trisomy-8 cells are equipped with other proteins that make them hard to kill -- they're armored! In the heat of battle, with the T-cells piling up and launching futile attacks agains the Trisomy 8s, one or both of two bad things happen: the T-cells start mistakenly attacking some of the normal, garden variety stem cells; or cytokines and other nasty stuff released in the battle between the T-cells and the Trisomy-8 cells start damaging the good stem cells and preventing them from doing their job: making usable red blood cells, white blood cells, and platelets.
]It's just like a real war, where there's "collateral damage," whether from misdirected drone attacks or land mines left lying around for innocent folks to step on. Civilians are wounded and killed.
Even though the T-cells aren't very effective at killing off the Trisomy-8s, they may sometimes damage them, possibly creating more -- and more problematic -- chromosomal abnormalities. That could turn lower-risk MDS into higher-risk MDS over time.
The solution to this problem that the folks at NIH have spent a lot of time exploring involves putting an end to the war, so the collateral damage stops and the civilians can get back to making good blood cells.
They do this not by attacking the Trisomy 8 cells, but by shutting down the immune reaction, using drugs called immunosuppressants. One strategy folks have tried for this is using cyclosporine; but that, on its own, hasn't proven too effective. So one accepted alternative that NIH pioneered is to use a few big doses of ATG, an immunosuppressant derived from horses or rabbits, to knock the immune system flat. That's followed up with cyclosporine, to keep it suppressed. This ATG/cyclosporine regimen is an accepted option for treating certain types of MDS patients and is included in the National Comprehensive Cancer Network treatment guidelines.
The main downside of this strategy is that ATG is a really big gun, basically knocking down all the different kinds of T-cells and leaving the patient seriously open to infections of all sorts. But the NIH folks have evidence that it's really only two specific kinds of T-cells that are involved in this war with the Trisomy 8s. Campath is a drug (derived from rat) that attacks only those T-cells. Folks who take it still wind up with the immune system of an AIDS patient, but mostly have to worry about viruses and one rare type of pneumonia, rather than everything under the sun. Folks participating in NIH's Campath clinical trial take some anti-viral drugs and a special anti-pneumonia treatment to fight off infection for the year or so it takes their T-cells to come back.
When the T-cells do come back, if all goes well, they are more tolerant of the Trisomy 8 cells and the war doesn't crank back up again. Even though the T-cells attacked them, it's not really clear that the Trisomy 8 stem cells are incapable of making good blood. Without the war, they may be able to happily co-exist with their garden variety stem cell brethren, all happily making blood together.
So which MDS patients are likely to have this odd immune system war going on? Different studies of immunosuppressants and MDS have produced different answers, including the following: Younger patients (50s or younger), with Trisomy 8, hypocellular marrow, positive for the HLA-DR15 marker on their white blood cells, not too many transfusions yet, and a couple of other factors. I have all of these characteristics, which means I have a high probability of response to treatment with Campath.
For the NIH trial, the key eligibility factors are age, HLA DR-15 status, and how long you've been getting red blood cell transfusions. The details are on clinicaltrials.gov
here. NIH has almost filled its recruitment goal for this trial, but may extend it.
There's a new study of Campath in MDS (and other bone marrow failure diseases) now recruiting at MD Anderson in Houston. That info is
here.
[Disclaimer: I have no relationship with Campath or its manufacturer or NIH or MD Anderson other than as an MDSer looking for the best answer to whip this lousy disease!]