CMV Infection: Less of a Risk Factor Today
One of the most frequent infectious agents in the wake of transplantation is cytomegalovirus (CMV). CMV belongs to the group of herpes viruses and about 80% of adults are carriers. Whether or not CMV disease develops after transplantation depends on many things, especially whether or not the stem cell donor and patient are carriers of the virus. The best possible scenario is when the donor and recipient are both clean, neither of them has been exposed to this nasty critter ever in their lives.
Cord blood is only very, very rarely CMV positive and therefore it boils down to whether or not the transplant patient has been exposed to this virus at some point in his life. As with many herpes viruses, if you have ever been exposed to it, even without knowing that you have been exposed, you will retain a small sample of this virus hidden away in your body and you will be at risk of this virus raising its ugly head for the rest of your life. The baby (cord blood) immune system cells coming in have never seen this beast, don’t know how to deal with it, and that means trouble if they run into this critter in their new home. CMV reactivation is a serious risk factor in cord blood transplants and something they take very seriously here in U. of Minnesota Fairview hospital.
Over the last ten years or so we have become a lot smarter about managing the risk of CMV infection in HSCT (hematopoietic stem cell transplant) patients. So much so that the incidence of this infection has dropped from 20-30% ten years ago to 5-10% today. Poorly controlled CMV reactivation in a transplant patient can be fatal. Acyclovir is a relatively cheap drug that can be used as prophylactic medication against CMV, but it has to be given in fairly hefty doses. Harvey is getting 10mg/kg of the stuff, twice a day.
Gancyclovir is more potent and the drug most frequently used against CMV. Typically, it is given by intravenous methods. Since Gancyclovir is eliminated by the kidneys, the dose has to be adjusted to the patient’s kidney function. Unfortunately it is not very well absorbed as a pill (less than 6%) and people have to take a lot of the pills if they are to get an adequate dose orally. However, it is very important to take the whole dose you are supposed to take, like it or not, because otherwise you will be running the risk of developing gancyclovir resistant version of the bug – not a good idea at all. For those unlucky souls for whom gancyclovir does not work, Foscavir is the next best option.
Here is a link to an excellent mini review article on the subject of CMV reactivation, specific to all blood stem cell transplant patients (not just cord blood transplants). If you are in the market for a stem cell transplant of any kind, this is an article worth reading, or at the very least filing away on your hard drive for when / if it becomes a pressing issue. Patients are most at risk if they have been treated with a T-cell depleting drug (read fludarabine, Campath, ATG), or if they are under immune suppressing therapy (cyclosporine, MMF, tacrolimus etc) to control GVHD.
When patients are evaluated ahead of the transplant, one of the things they check for is CMV status. They do this by looking for antibodies (immunoglobulins, Igs) against CMV in the patient’s blood. These CMV specific immunoglobulins are tell-tale markers that when present indicate the patient’s body had a close encounter with the virus at some point in its prior history and therefore had to develop immunoglobulins to fight the virus. Detection of CMV-IgG and CMV-IgM in the blood is taken as proof of prior CMV exposure and therefore higher risk of reactivation down the road.
Funny thing happened with Harvey. I am not completely sure, but I have some tentative reason to think he is actually CMV negative, based on a test done several years ago. However, just prior to coming to Minneapolis for the transplant, Harvey had his regularly scheduled IVIG (intravenous immunoglobulin) therapy to try and prevent infections of any kind while we were travelling from Sedona to Minneapolis. Guess what. The immunoglobulins given in IVIG therapy are derived from the pooled blood of community volunteer donors. Since roughly 80% of adults in this country are CMV positive, it goes without saying that most of these generous blood donors are going to have immunoglobulins directed against CMV in their blood. When immune deficient patients like Harvey get IVIG therapy, they are “borrowing” strength from the lessons learned by the immune systems of healthy blood donors in their community. That is the whole point of doing IVIG therapy.
In other words, whether or not Harvey had been actually exposed to CMV virus at some point in his life, the fact that he has had IVIG therapy may be all the reason why he tested positive for this blood test. He may have the best of all possible scenarios, no traces of the actual virus itself in his body if he had never been exposed and therefore no potential risk of viral reactivation down the road, but lots of community acquired Ig protection against it because of his IVIG therapy. Also, the positive blood test for CMV-Ig means Fairview Hospital has him classified as “at risk” patient and therefore they go the extra mile in trying to prevent any possible reactivation – as in higher dose of anti-viral therapy and more robust monitoring for any sign of CMV reactivation.
As part of the “at risk” patient monitoring, they look for viral load (number of copies of the virus in the blood) by means of pcr testing each week. Harvey has tested negative for this the last two weeks. So far, so good on this front.