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A Trade or Two

Posted by Frederick Wasti
Apr 15 2012

A stem cell transplant (an "SCT") represents a trade - or, actually, I guess it may represent two trades, as follows:

In one sense, if I were to submit to an SCT procedure, I would be trading in my own immune system, in return for the immune system belonging to some unknown matched donor. The success of an SCT would require that my own immune system be disabled, in order that my body would not reject the donor's stem cells given to me. This would necessitate a few days of chemotherapy just before I would be given the transplanted cells. (Dana-Farber happens to generally use the drugs Fludarabine and Bisulfan for this, and, interestingly, each of the major SCT centers uses a somewhat different "cocktail" for the purpose).

Upon the introduction of the foreign donor cells to my body, a battle would then ensue - my own immune system cells would try to destroy what they would detect as "invaders", while the donor immune system cells would attack my own cells as being "foreign" to them. In an ironic twist, I would then likely be rooting for the donor blood cells to win and for my own blood cells to lose - if my own cells did succeed in destroying the donor cells, the transplant would end up failing (and that's why the Fludarabine and Bisulfan are used - to "stun" my immune system into not responding to the invaders, so that the invaders might not be rejected).

However, if my own immune system's cells remain passive after I am given the donor cells, the donor cells would hopefully succeed in destroying their competitors (i.e., my own blood cells, but, most importantly, my aberrant leukemia cells, too), and they would proceed to make my body their new home. So, I would have ended up trading in my own immune system for someone else's. Well, that represents trade number one.

Now, in order to explain the second trade, I will first have to try to explain a couple of new terms (well, they may or may not be new to you, but I can certainly say they are somewhat new to me):

First, there is something called the "Graft versus Leukemia" (or "GVL") effect to consider. This is the reason why stem cell transplants are performed on people having leukemia. Remember that the main problem in leukemia is that an increasingly larger and larger number of leukemic white blood cells (that started out as just one cell that mutated and then started reproducing uncontrollably) are "accepted" by the rest of the cells in the body (or, in the case of CLL, the aberrant lymphocytes can also "hide out" in safety in the spleen and the lymph nodes). That is to say that the leukemia victim's own body does not adequately defend itself against the cancerous blood cells within - the cancerous cells are (most of the time) able to avoid detection as being as dangerous as they are by the immune system.

However, as a result of a successful SCT, the donor cells "grafted" into a new body do not feel so "kindly" toward the leukemic white cells (or to any of the other white cells, either - that was trade number one, you may remember) - in fact, the donor cells will try to destroy all the leukemia cells, and this particular positive effect is where the name "Graft versus Leukemia effect" comes from. It should be obvious that ~this~ would represent the hopeful outcome from a successful SCT.

But, there is also something referred to as "Graft versus Host Disease" (or "GVHD") to consider as well. The same donor cells that would now be busily judging leukemia cells to be fully deserving of being destroyed will also tend to find the rest of the host's body cells to be at least somewhat foreign, too, and may cause problems if they try to reject their host (even though it is now their home, but they may seem not to "know" that). The resulting GVHD might be chronic in nature (resulting in such things as skin inflammation, gastrointestinal tract irritation, etc.), or it could even be acute.

The nature of the match between the host blood cells and the donor cells is important, but - perhaps surprisingly, until one thinks about it - the match must ~not~ be "too good":

It should be clear that, if the match were to be poor, the damage done by the host cells to the donor cells (even though the host cells have been "stunned") could result in rejection of the transplant. Or, the opposite could occur - the donor cells might wreak havoc on many of the cells in the host body (acute GVHD). Obviously the match should ideally be close enough that neither of these events occur.

However, the match between host and donor cells ~cannot~ be "too close", either. If one thinks about it, a "perfect match" (such as would occur if the transplant occurred between two genetically identical twins), would make the transplant ineffective. If the host's own immune system had been "tolerating" aberrant leukemia cells for some time already, then genetically identical donor cells would likely also be just as "tolerant" - in this event there would ~not~ be any Graft versus Leukemia effect at all, causing a seemingly successful transplant (i.e., one that was not rejected, and did not cause any GVHD to occur, either) to be essentially ~useless~, since no leukemic cells would end up being destroyed.

So, there has to be a balance - the match between donor cells and host cells must be close, but not too close - there has to be a compromise between GVHD and GVL. In other words, a successful SCT would take away leukemia, but it would also replace it with another disease - Graft versus Host Disease. And that is trade number two - the patient in a successful transplant trades in their leukemia for a hopefully more manageable disease, GVHD.

Sometimes life can indeed be a compromise... :-)

[Please note - I have not been talked into having a stem cell transplant yet - the above is just the result of having to think about it and research about it.]

Categories: Leukemia