High-Dose Therapy and Allogeneic Transplant: Infection Control

I am Dr. Harry Erba. I’m a professor of internal medicine and director of the Hematologic Malignancy Program at the University of Alabama at Birmingham, in Birmingham, Alabama. Joining me today are my distinguished colleagues. To my right, Dr. Roy Chemaly, professor of medicine, director of Infection Control Section, and director of clinical virology in the Department of Infectious Disease at the University of Texas, MD Anderson Cancer Center in Houston, Texas. And to my left, Dr. Mark Levis, program leader of Hematologic Malignancies and Bone Marrow Transplant at the Sidney Kimmel Comprehensive Cancer Center, and professor of oncology at Johns Hopkins University in Baltimore, Maryland. Thank you so much for joining us, let’s begin.

So, Mark, I’d like to start with you. Describe for me why there is a need for infection control in patients receiving high-dose chemotherapy, ablative therapy, and undergoing stem cell transplant.

Mark Levis, MD, PhD: Well, it should be remembered that while the patient is frequently in remission going into an allogeneic transplant, or stem cell transplant, what it took to get them there is another matter entirely. They almost certainly have experienced either a bacterial infection, an invasive mold infection, or reactivation of a virus during the journey to even get to that point. And have we truly fully eliminated or eradicated that infection prior to the transplant? Probably not. Now they’re going to go into that transplant procedure and become even more profoundly immunocompromised, and, in fact, in new ways typically affecting the T cell compartment. It’s unfortunately, a whole new opportunity for these infections to hit. So, without paying attention to this, you just would never get these patients through safely.

Harry Erba, MD, PhD: And so, clearly the patients coming to you for stem cell transplant are quite a mixture of prior disease states, therapies, other infections, age, and comorbidities. In your mind, is there some way that you risk stratify these patients, and does that affect your prophylactic measures?

Mark Levis, MD, PhD: Of course. In fact, even starting the patients who have had a prior fungal infection or specific infection, typically we’ll consult our infectious disease colleagues to say, “OK, this patient’s already had aspergillosis, pulmonary infection, or where have you. How are we going to prevent this from recurring? What’s our strategy going into the transplant?” Just that alone, there’s a prior established infection. Second, the degree to which they got it, that you had to treat them to get them to the point where they’re going to undergo transplant. So, frequently, we might choose transplant for a second remission or somebody who had gotten back into remission after they’ve relapsed. That person has already had multiple rounds of intense immunosuppression, so they’re at higher risk.

Now finally, and this pertains specifically to the acute leukemia patients, going into transplant with any minimal residual disease predicts for a poorer outcome from allogeneic transplant. But, interestingly, what many people don’t realize is it’s often due to an increased death rate during the transplant, specifically from infections.

Harry Erba, MD, PhD: Not relapsed?

Mark Levis, MD, PhD: No.

Harry Erba, MD, PhD: That’s interesting. If we had more time, we’d talk more about that today, but I want to move on to other topics. Now when I think about my patients—I’m not a transplanter, as you know, and I send to transplant—the things I’m most concerned about are fungal infections and CMV (cytomegalovirus). These are the problems that they seem to have. But, I don’t want to forget about the bacterial infections that these patients may also get. So, is there a bacterial prophylaxis that you use in patients undergoing transplant? I’ll let you answer that, Mark.

Mark Levis, MD, PhD: At our institution, this, of course, was a matter of intense debate, and it went on for months. I was part of that debate. Certainly, gram-negative rods need prophylaxis against, and everybody could agree, a fluoroquinolone. That was the best choice there for that. It was the question of whether or not we could get away with just a penicillin, and even which penicillin we would use. I’ll defer that to our infectious disease colleague to come down on the answer for that. So, certainly just bacterial, both gram positive and gram negatives, need to be covered.

Harry Erba, MD, PhD: And this is going to date me, but I remember the days when we gave oral nonabsorbable antibiotics to cleanse the gut. Do we do that anymore?

Roy Chemaly, MD, MPH: No. Actually, it’s not a routine practice at the present time, and the reason is the rate of resistance by doing this kind of strategy is pretty high. Unfortunately, the bacteria adapt rather quickly to any shred that they are exposed to, and they become resistant to these nonabsorbable antibiotics. I also would add that for bacterial prophylaxis, you have to know what’s going on in your institution, what kind of multidrug-resistant organism that you encounter the most. And this is how you sometimes base your prophylaxis regimen, although most of us will still recommend fluoroquinolones because you want to mainly prevent shared virulence from a patient with oral mucositis from a conditioning regimen for their allogeneic transplant, or enterobacteriaceae as well when they have ulceration from their chemotherapy. So, this will work pretty well, although we see some breakthrough infection, unfortunately, because of the resistance for some.

Mark Levis, MD, PhD: And that’s becoming a real problem. We’ve had several patients develop multi-drug resistant gram-negative rods where literally we have a conference on each patient—what’s our strategy for preventing recurrence of this organism during transplant?

Harry Erba, MD, PhD: So, it’s gotten very complicated, obviously.

Transcript edited for clarity.

Harry Erba, MD, PhD: Hello, and thank you for joining this MD Magazine^® Peer Exchange^® titled “Optimizing Infection Control to Improve Outcomes of Allogeneic Stem Cell Transplant.” Infection is a serious, potentially life-threatening complication for immunocompromised patients, particularly those who undergo myeloablative therapy and allogeneic hematopoietic stem cell transplantation. In this MD Magazine® Peer Exchange® panel discussion, my colleagues and I will discuss the latest information regarding optimizing infection control to improve outcomes in transplantations.