Fighting the complications of influenza

One of the populations at greatest risk for severe complications from flu infection is a group that cannot be successfully vaccinated against the influenza virus: cancer patients who recently have undergone bone-marrow or stem-cell transplantation. A new study from the Clinical Research Division now finds that administering antiviral drugs at the earliest signs of flu infection in transplant patients significantly reduces their likelihood of developing pneumonia, a potentially fatal complication.

The study identified the most effective flu-fighting drugs for this population, results that are expected to improve overall survival rates for transplant patients by minimizing the likelihood of influenza-related deaths, said Dr. Michael Boeckh, a co-author of the study. Transplant patients have severely weakened immune systems for several months after the procedure, making it difficult for them to fight off viral, bacterial and fungal infections during the recovery period.

"Our results show that if pneumonia develops after a flu infection, it poses a very big mortality risk for transplant patients," he said. "However, we found that this risk can be significantly reduced by treating patients who have the flu with a specific class of drugs that inhibit virus and prevent the infection from progressing to pneumonia."

The study appears in the November 1 issue of Clinical Infectious Diseases. Co-authors include Dr. W. Garrett Nichols, a former associate in clinical research, and Drs. Katherine Guthrie and Larry Corey, both investigators in the Clinical Research Division.

Infections with respiratory viruses such as influenza are thought to be major causes of complications and death in patients who have undergone bone-marrow or stem-cell transplantation for leukemia or other blood cancers. Clinics including the Seattle Cancer Care Alliance use aggressive efforts to prevent patients from ever becoming infected. Even with this year's vaccine shortage, Alliance health-care workers who have direct contact with patients and patient family members receive free vaccination provided by Fred Hutchinson or the clinic. To further prevent widespread outbreaks in the clinic, caregivers in direct contact with patients who are infected with respiratory viruses wear protective gloves and gowns to prevent transmission to others.

"We also restrict caregivers who are sick with a respiratory virus from directly working with bone-marrow or stem-cell transplant patients," Boeckh said.

Patients are not vaccinated, he said, "because at the early stages of transplant recovery — which is the time patients are most vulnerable to infection — the immune system is not mature enough for vaccination to be successful." The transplant procedure involves eliminating the patient's own cancerous immune system with high doses of radiation and chemotherapy followed by infusion of donor cells to reconstitute a healthy immune system, a process that takes several months.

Neuroaminidase inhibitors

Although these preventive measures can significantly reduce influenza outbreaks, some patients do develop infections. In the current study, the researchers reviewed records of 4,797 patients who underwent transplants at Fred Hutchinson or the Alliance during a 13-year period. Among the patients, 62 individuals (1.3 percent) developed influenza virus infections. Forty-four of these cases affected only the upper-respiratory tract, while 18 individuals developed pneumonia.

The researchers found that patients who developed pneumonia had more than two-and-a-half times the risk of dying compared to patients who did not develop pneumonia. A small subset of patients with upper-respiratory tract infections who were treated with a class of antiviral drugs known as neuroaminidase inhibitors developed very few cases of pneumonia. These drugs, marketed under the trade names Tamiflu and Relenza, inhibit a protein on the surface of the influenza virus, which prevents the virus from spreading within the body. Both drugs have received approval from the United States Food and Drug Administration for treatment of the flu as well as prevention of flu infections in those in close contact with infected individuals.

In contrast, antiviral drugs known as M2 inhibitors appeared to be less effective against preventing pneumonia in transplant patients. The one-year mortality rate for those treated with the neuroaminidase inhibitor oseltamivir was 0 percent compared to 40 percent for those treated with rimantadine, an M2 inhibitor.

In addition to preventing pneumonia, treatment with oseltamivir decreased the amount of virus shed from the respiratory tract. The amount of shedding influences the likelihood that the virus will be transmitted to others.

Boeckh said that although the numbers of patients in this study were small, the results show that effective treatments are available for those who develop flu infections despite aggressive prevention strategies.

"Vaccination is not 100 percent effective, and in any given year, the vaccine may not be protective against the most prevalent strains," he said. Boeckh said that the viral strains included in this year's vaccine appear to match those infecting the population at large in the United States at this point.