Panelists:Rafael Bejar MD, PhD, UCSD Moores Cancer Center; Elias Jabbour, MD, MD Anderson Cancer Center; Rami S. Komrokji, MD, Moffitt Cancer Center; Ruben A. Mesa, MD, FACP, Mayo Clinic Cancer Center
Ruben A. Mesa, MD, FACP: Elias, you brought up earlier an excellent point and a segue into our last key section on the issue of support infection and all other aspects. And we’ve had a good discussion regarding how there’s been significant effort and hopefully advance in terms of how we target the leukemia clone. There are several key things that I’ve observed in my career. For one, therapy: patients have to be able to take the therapy. If they’re really not able to tolerate what’s a very complicated course of therapy, then their outcomes are tremendously compromised. This is the patient for whom everyone is focused on the transplant but doesn't make it to the transplant because they develop an Aspergillus pneumonia or some other catastrophic event.
I recall early in my career I had a patient with APL that was told they had the good-risk leukemia by one of the residents, who ended up dying of mucormycosis along the course. So, clearly, there are a lot of other factors. So why don’t we break down a little bit of that supportive care discussion in terms of what really are best practices in terms of trying to prevent infections, as well as other aspects of support? Rami, why don’t you start us out. In terms of your standard leukemia patient at Moffitt who’s in there, what is your guys’ approach to their supportive care?
Rami Komrokji, MD: I think you bring up an excellent point, and I think that’s what I am most of the time: teaching the residents and fellows on service when they are attending the leukemia service. There are things we do early on. The APL is a great example. Those are patients that are expected to do well, but there’s always that 10% to 15% mortality. And if you look at that mortality, that’s always the setting of the induction, either infection or bleeding. So I think we can break it into different things. So, obviously, at the disease point itself, we have things like complications of leukostasis, high white count. That usually heeds some supportive care to control the counts. Some patients that come in with leukostasis manifestations may need leukapheresis at the beginning. There are the bleeding issues, whether we are in DIC (disseminated intravascular coagulopathy) or not. So, that’s one aspect.
And there is obviously the supportive blood transfusions for patients, which is actually also a debatable point. When do you transfuse? What’s the threshold for hemoglobin? Do you really need to transfuse every patient below a 10? For platelets, there were some nice studies from the Canadian group presented on that. But then the major issue in patients with AML induction is the infection. Obviously, those patients are immunocompromised, and now we’re introducing an intensive chemotherapy that causes mucositis. That’s a recipe for getting infection. I tell patients I can count on my hands the people that do not have fever. I doubt there is anybody that doesn’t get febrile neutropenia with intensive chemotherapy.
So I think that prophylaxis is a key, and what we’ll do as a standard is triple coverage. We’ll do antibacterial coverage. We’ll do antifungal and antiviral. Our infection disease group is actually aggressive. They’ll do even baseline CT scans, and they will repeat CT scans earlier, sometimes based on presence of nodules. They will intervene and change the antifungal coverage based on that, and they’ve published some of that that actually led to less diagnosis of invasive fungal infections. We culture those patients whenever they have fevers.
We change the antibiotics accordingly. I think we all look at the AML patients, and in my mind, sometimes many of those patients are neutropenic for a while and they are at risk of infection. But we’ve seen some improvement, and some of the improvement we see in management of those patients is maybe due to the newer antifungal agents, the better antibiotics we have that had reduced the rate of infections for those patients. It’s always a challenge, for the fungal infections in those patients, of being certain that they have the infection or not. So, many times we are treating a presumptive infection because you cannot take the risk.
Ruben A. Mesa, MD, FACP: I hear about the five leukemia services with 20 patients each on them at MD Anderson. What is your sense, in terms of this burden, of the infected patient? How much morbidity/mortality do we expect with that? How prevalent is that?
Elias Jabbour, MD: I think leukemia patients should be treated by experts, it should not be in the community, because it makes a difference. Tuning of minor things, supportive care, it makes a huge difference. For example, I had a patient, and he was given ATRA nonstop, and the guy had white lungs. And what you have to do is stop the treatment for a few days and let him recover. We brought him to Anderson. He went to the ICU. He recovered, came back to our floor, and he’s cured now. But tuning things is really important.
Now, in AML, we mentioned the hidden life of cancer. The immune system is compromised. The neutrophils are dysfunctional. And you know from MDS background, even if you have an ANC [absolute neutrophil count] of 1000, it doesn’t mean they have a good immune system. And therefore, we’re being very aggressive with antibiotic and antifungal therapy. Now, we have an environment where we have mold, yeast. Which one you pick first? And then you have a decision to make. Some have a preventive use label, some others don’t. We know that financial burden for these treatments. We know they’re getting acute leukemias, they have mucositis, they cannot absorb. You give azoles, you check the level, you give other families, but you need to be very aggressive.
I had a call one day at night. I had somebody with neutropenic fever going to the local ED and the doctor said, ‘Well, shall we wait for the culture to start antibiotic?’ No, you don’t. Empirically, we have been very aggressive with antibiotics, antifungal therapy, azoles. And one more thing that’s important with the azoles and others—when we give this ABT-199, new agents, IDH2 inhibitors—there’s a lot of interaction, QT prolongation. You give antibiotics, you give a TKI, you give something else.
The FDA is very cautious about telemetry QT prolongation, so be very careful. As Rami mentioned, use CT scans. There’s data published on PET scan. So we’re really going beyond what the normal practice does in order to be preemptive and have a good treatment. Especially, as you mentioned, most of our patients still get labs. And when they go for transplant, they say, ‘but he had fungal pneumonia, what do I do?’ Delay transplant? Delay transplant, and then guess what? The patient is progressing again. Having aggressive intervention and being preemptive is really the key for success.
Transcript Edited for Clarity