Morbidity from CMV Infection in Transplant Patients

Harry Erba, MD, PhD: Let’s turn now to the other major infectious problem that our patients post allogeneic transplant are facing, and that’s CMV. So, first of all, Mark, from the clinical perspective, what is the importance of even preventing CMV viremia? We have drugs, so now what?

Mark Levis, MD, PhD: CMV used to kill a large fraction of transplant patients. It would occur, in a mysterious fashion, months after the transplant. We didn’t know it was there. Our assays for it were primitive really. It actually, in retrospect, was a terrible plague in those patients. Now we have a methodical approach to addressing the problem, a very fixed protocol for beginning serial monitoring for reactivation of CMV. But, of course, we pay attention to that even pretransplant. The status between the donor and the patient is quite important as well.

Roy Chemaly, MD, MPH: So, if I may add also, CMV is a very interesting virus actually. By itself, it’s an immunomodulator. It can cause immunosuppression as a vital infection. But, also before their preemptive therapy, we used to see much more end-organ disease, and mainly CMV pneumonitis.

Mark Levis, MD, PhD: Yes, the culture negative pneumonias.

Roy Chemaly, MD, MPH: Right, before we had the tools to diagnose this kind of infection. And it is a serious infection if somebody gets it after transplant, with very high mortality. And the reason is we used to do prophylaxis, meaning giving drugs at the start of engraftment for a patient with a problem that we had, and we still have. Hopefully, after we get new drugs on the market, there won’t be toxicity from the drugs commercially available.

So, we’re talking about ganciclovir or foscarnet. Ganciclovir is a myelosuppressive drug, we know that. And I know the transplanters don’t like it at all. They don’t want to go there. But, at the same time, the alternative is foscarnet, which is a very toxic drug to the kidneys unless you monitor the IV fluid and the electrolyte very closely. You can get nephrotoxicity from it. That’s why we move away from prophylaxis, I would say, because of this toxicity to preemptive therapy where you look for CMV, viral load in the blood once a week, sometimes twice a week. If it’s positive, you treat short course, and then you go back to your preemptive therapy—try to mitigate a little bit the toxicity from these drugs.

Mark Levis, MD, PhD: But, what I have to tell my patients is, “OK, once we get you through the first month and you’re engrafted, and the second month comes, there are things we’re looking for. We’re looking for graft versus host, but CMV reactivation.” And that’s a real drag.

Harry Erba, MD, PhD: Right, and that I was going to ask, is there a risk period? I understand there’s a risk period for all of these different infections, but for CMV, what’s the risk period?

Roy Chemaly, MD, MPH: CMV, actually, is a very common infection for a recipient who is CMV seropositive. They’ve been exposed to the virus, it’s latent infection now in up to 80%—or sometimes if you ask some cord transplant centers, they will tell you it’s 100% in cord and haplo-cord transplant. So, you stratify by high risk versus low risk, even match-related donor transplants, which usually are at low risk for any kind of infection, but CMV is still up to 50%. So, we’re talking about a high percent of the patients going to get CMV reactivation. And now we’re going to use all these toxic drugs, put them at a disadvantage. Actually, looking at data from Michael Boeckh from Fred Hutchinson Cancer Research Center, looking only at any CMV viremia with PCR 250 U/mL or above puts patient at disadvantage for survival when you compare to the ones who did not have CMV viremia.

Mark Levis, MD, PhD: I’ve seen patients have grafts rejected with out-of-control CMV reactivation. Certainly, they have died from it. And it’s just a tremendous cause of morbidity when then you have to add the ganciclovir. They’ve just engrafted, they’ve finally gotten off transfusions, and everything plummets.

Transcript edited for clarity.