Hematopoietic Stem Cell Transplant: Infection Control - Episode 9
Roy Chemaly, MD: For preemptive therapy, as I mentioned earlier, you wait for the positive test. We use the viral molecular assay, which tests for viral load by PCR [polymerase chain reaction] at a certain cutoff. Every center has a different cutoff, I would say. At our institution, for high-risk patients—usually defined as patients who received a cord blood transplant, haploidentical transplant, or mismatched unrelated donor transplant or got ATG [antithymocyte globulin] as part of their conditioning regimen—we wait until we see a threshold of 500 or above to start treatment.
For lower-risk patients who are still recipient-positive for CMV, who may have received a matched related donor transplant, don’t have graft-versus-host disease, are not on a high-dose steroid, and didn’t receive T cell—depleting agents, we wait until the viral load goes above 1000 before we start preemptive therapy. So, there are 2 different cutoffs. It depends on the patient risk factors for CMV reactivation, progression, and end-organ disease. Other centers may use lower or higher thresholds. There is no consensus as to which threshold of CMV viral load should be used to initiate treatment. It’s arbitrary based on our experience and other expert experience. That’s how we define it in our institution.
I think we are overtreating patients with low levels of reactivation. In some instances, we don’t feel comfortable with observing and watching the patient until the viral load goes up higher. Sometimes, we jump the gun and we start treatment. We did a study, which didn’t publish yet—it’s under review—where we looked at this low level of reactivation, especially where you detect CMV in the blood but it’s not quantifiable, or is borderline, and we observed these patients. We did an ELISpot [enzyme-linked immunospot] T-cell assay to look for CMV-specific responses in these patients, to see if this could help us identify patients who are at risk for progression.
We found interesting results. Patients with high ELISpot T-cell response—meaning they had a positive result, indicating that they had enough CMV-specific T cells circulating—were actually protected against progression, even without treatment. These patients had a self-resolution of viremia without treatment. Most patients with lower CMV-specific T-cell responses progressed. They had higher levels of antiviral load, down the road, and needed to be treated.
In the future, we may have a tool to help us determine patients who need to be treated—if they have a low level of CMV reactivation or are at risk for progressing to a higher level of reactivation or CMV end-organ disease. But, there’s still no commercially available test for CMV-specific T-cell response. It’s all done under research, in research labs. But, in the future, this can play a role in helping us to determine if a patient needs to be treated or not. Because, as I mentioned earlier, some of these patients may not need to be treated. Their immune system will take care of this low level of reactivation.
Currently, most of the centers use a preemptive strategy to address CMV infection after hematopoietic stem cell transplantation. And, as I mentioned earlier, we monitor CMV by PCR in the blood plasma on a weekly basis. Sometimes, we do this twice a week in the high-risk patients during the high-risk period, which is usually between day 0 and day 100 from transplant. Sometimes, we do this even longer, if they have acquired additional risk factors for CMV reactivation, like graft-versus-host disease, or are on high-dose steroids. This is the main strategy that we follow.
As soon as we have a positive test above a certain threshold, we start treatment with one of the drugs that I mentioned earlier—ganciclovir, valganciclovir, or foscarnet. We know they are effective. They will have an impact on CMV reactivation, but they are toxic drugs. With ganciclovir and valganciclovir, we talked about myelosuppression. It could be serious. Patients may lose their graft if you continue treatment with this drug. Foscarnet can cause electrolyte imbalance, which also can be serious, as well as nephrotoxicities.
So, these drugs have many drawbacks, including toxicity, as I mentioned earlier. That’s why we need better strategies. We need better drugs. We need safer, effective drugs for the prevention of CMV reactivation.
Transcript Edited for Clarity