Expert Perspectives: Management of Acute Myeloid Leukemia - Episode 16
Yoav Golan, MD, MS, FIDSA, attending physician and associate professor of medicine at Tufts University School of Medicine, Boston, MA, discusses common viruses that may reactivate in patients with acute myeloid leukemia (AML), highlighting that preventative approaches that should be taken.
Among the pathogens that can determine the outcome of AML treatment are viruses. Viruses are abundant in the environment and are often carried in our body. Immunocompromising agents that we use to treat AML not only increase the risk of bacterial and fungal infections, but also viral infections, particularly those viruses that are carried in our body or that infected us in the past.
The most common viruses to cause trouble in AML patients belong to the herpes family of viruses, mostly Human herpes virus 1 (HHV1), chicken pox virus (or varicella zoster virus (VZV), and cytomegalovirus (CMV). While most patients who develop AML and undergo therapy have been exposed to the chicken pox virus in their childhood or received vaccination against chicken pox, many are colonized and carry the herpes virus that commonly causes cold sores in people who are not immunocompromised. And about 50% to 60% of adults have also been infected by CMV in the past and continue to carry this virus as well.
The use of immunosuppressive therapy as well as the disease itself are major risk factors for reactivation of those viruses which means that those viruses lose their immune control and can start replicating and causing disease. Disease caused by those viruses very often is very different from disease caused by the same viruses in immune-competent patients because of the lack of immune control.
So, for example, Herpes simplex virus that commonly causes cold sores in other people can cause disseminated herpes disease that can affect many internal organs, particularly the liver and others, and can be lethal in many of the patients who develop it. Another example is CMV that can reactivate in a patient who is immunocompromised and cause multi-organ disease that includes the eyes, lungs, bone marrow, and kidneys. Reactivation of those viruses is not infrequent in our patients.
The first step in preventing those infections is adequately classifying the patient as being at risk by doing a few blood tests to look at serologies for HHV 1, other herpes viruses, antibodies to VZV, and antibodies to CMV. Those patients who have been infected and have positive antibodies should receive antiviral prophylaxis. It was shown that antiviral prophylaxis in those patients will reduce the risk of infections by herpes viruses. The choice of antiviral prophylaxis varies from one center to the other with the most commonly used agents including acyclovir, valacyclovir, and Famvir as well.
Antiviral prophylaxis is usually given starting at the beginning of neutropenia and followed all the way to the end of neutropenia, and in those patients with specific risk factors such as severe mucositis or being on immunosuppressive agents such as steroids for a very long period of time, antiviral prophylaxis should be longer and cover this vulnerability period as well.
As we mentioned, CMV is actually one of the viruses that could be very problematic in immunocompromised patients, particularly in AML patients and patients undergoing bone marrow transplantation. One of the issues in preventing CMV disease is that the most effective agents, ganciclovir and valganciclovir, are also potent suppressors of the bone marrow.
One of the parameters that determine the outcome in patients with AML undergoing chemotherapy and those who get a bone marrow transplant is their ability to engraft and resolve their neutropenia. Obviously, ganciclovir and valganciclovir can interfere with that. For those reasons, those agents are now typically used as standard prophylaxis for CMV.