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May 2009
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Flu Vaccination in Patients with Cancer

During the 2006–2007 season, influenza circulated at epidemic levels for about 14 weeks and peaked during February, the month most frequently associated with peak activity over the past 31 influenza seasons.

Influenza epidemics occur every year in the United States, typically beginning in the late

fall or winter and concluding during the spring.1 During the 2006—2007 season, influenza

circulated at epidemic levels for about 14 weeks and peaked during February, the month

most frequently associated with peak activity over the past 31 influenza seasons.1,2 According

to estimates from the Centers for Disease Control and Prevention (CDC), influenza has

caused roughly 36,000 deaths and 226,000 hospitalizations annually.3,4 However, the rate

of flu varies each year based on viral virulence and duration of circulation. Complications,

hospitalizations, and death are most common in patients aged =65 years.5,6 In recent years,

there has been a growing recognition among oncologists and other cancer care professionals

of the importance of vaccination against influenza in patients with cancer.

For most people with cancer, vaccination for influenza is not only safe, but also a crucial part

of staying as healthy as possible. Owing to their weakened immune system, patients with cancer

are at high risk for infection with flu and pneumonia viruses, which can be lethal in these individuals.

Yearly flu and pneumonia shots often prevent infection entirely and can lessen the severity

of illness in those who do get sick.

Influenza Viruses

Influenza viruses are divided into three types, designated A, B, and C. Influenza types A and

B are responsible for epidemics of respiratory illness that occur almost every winter and are

often associated with increased rates for hospitalization

and death. Influenza type C differs from types A and B in some important ways.

Type C infection usually causes either a very mild respiratory illness or no symptoms at all;

it does not cause epidemics and does not have the severe public health impact that influenza

types A and B do. Efforts to control the impact of influenza are aimed at types A and B.

Influenza type A viruses are divided into subtypes based on differences in two viral proteins

called the hemagglutinin (H) and the neuraminidase (N). The current subtypes of influenza A

are designated A(H1N1) and A(H3N2). Influenza A(H1N1), A(H3N2), and influenza B strains are

included in each year’s influenza vaccine. In the years since its emergence, type A(H3N2) epidemics

have caused more than 400,000 deaths in the United States alone, and more than 90% of

these deaths have occur-red among people age 65 and older.

Influenza type A viruses undergo two kinds of changes. One is a series of mutations that

occur over time and cause a gradual change in the virus. This is called antigenic “drift.” This

constant changing enables the virus to evade the immune system of its host, so that people

are susceptible to influenza virus infection throughout life. This process works as follows:

A person infected with influenza virus develops antibody against that virus; as the virus

changes, the “older” antibody no longer recognizes the “newer” virus, and reinfection can occur.

The older antibody can, however, provide partial protection against re-infection.

The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase

proteins. This is called antigenic “shift.” In this case, a new subtype of the virus suddenly

emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only

by the more gradual process of antigenic drift.

CDC Recommendations For Influenza Vaccination

Influenza vaccination is the most effective method for preventing influenza virus infection

and its complications, which may be severe The CDC updated its recommendations

regarding who should receive influenza vaccination in 2008.1,7 Current recommendations

regarding annual vaccination in children/adolescents and adults are summarized in Table 1

and Table 2, respectively. It is important to note that patients with cancer may fall into several

of the categories shown in the tables.

In 2008, the Advisory Committee on Immunization Practices (ACIP) of the CDC expandedits

recommendations for influenza vaccination for school-aged children.1,7 The ACIP-CDC

now recommends that all children aged six months to 18 years receive annual influenza

vaccination, beginning in 2008 if feasible, but beginning no later than during the 2009—2010

influenza season.1,7

Since influenza viruses undergo frequent antigenic change, persons recommended for

vaccination must receive an annual vaccination against the viruses known to be in circulation

each year.

According to the CDC,1 trivalent influenza vaccine may be used for any person aged

=6 months, including those with high-risk conditions. The 2008—2009 trivalent vaccine

virus strains are A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like,

and B/Florida/4/2006-like antigens.1 Live, attenuated-virus vaccine is currently approved

only for healthy, nonpregnant persons aged 5—49 years.

Flu Vaccination in Patients With Cancer

According to the CDC, less than 30% of patients with high-risk conditions, including cancer,

were vaccinated against flu in 2005.8 Table 3 shows flu vaccination coverage levels in persons

with high-risk conditions, including cancer, by age. Data shown in the table were derived

from the National Health Interview Survey and National Immunization Survey, US, 2005.

The results of a survey presented on October 27, 2007 at the 49th annual meeting of the

American Society for Therapeutic Radiation and Oncology (ASTRO) in Los Angeles (Poster

2641) highlight the poor flu vaccination coverage in patients with cancer specifically.9 About

a third of patients who responded to an anonymous survey said they had not had a flu vaccination,

according to Neha Vapiwala, MD, University of Pennsylvania, Philadelphia, PA, and

one of the authors of the presented study. The survey was completed by 214 consecutive

cancer outpatients at the University of Pennsylvania from August 2006 to January

2007. Ninety-eight percent of the questionnaires were complete and usable for analysis.

This was the first performed to evaluate whether patients with cancer are compliant

with national vaccination guidelines. Patients who reported not receiving flu vaccine were

asked further questions about the reasons why they didn’t receive it.

Key findings from the study were as follows:

• Thirty percent of patients said they had never

had the flu vaccine, and another 9% said they

were not getting vaccinated yearly.

• About 60% of unvaccinated patients said they

didn’t know they needed a flu shot.

• Among patients aged 50 and older—i.e., those

recommended for a flu shot—33% had never

been vaccinated.

• Among patients who got their shots, 66% said

they heard about the vaccines from a health

care provider other than one providing cancer

care. Only ten% of patients were told about flu

vaccine by an oncologist.

Dr. Vapiwala reiterated, “Despite being seen by many clinicians for their cancer care, only one

in ten patients who actually got vaccinations said the shots had been recommended by their

oncologist.”

When asked about potential reasons for the suboptimal flu vaccination in patients with cancer,

Dr. Vapiwala explained, “It’s a communications gap. Oncologists tend to assume that vaccinations

are being handled by the primary care provider, while the primary care physician may

assume the opposite. It’s not clear to patients and it’s not clear to physicians necessarily who

is responsible for what.”

Clearly, a key reason for not receiving flu vaccine was not knowing about the vaccine,

thinking it was not needed, or not having it recommended by a physician. The issue is important

because patients who have malignancies and who undergo cancer treatment are at

greater risk of acquiring viral illnesses such as influenza. They also tend to have a more severe

course and a more difficult recovery once they develop an infection.

Although the study was small and focuses on a single institution, Dr. Vapiwala said she

thinks the communication gap is a general problem. “Somebody has to take responsibility

[for routine care issues], and right now, it’s a gray area.” She added, “Oncologists have the

opportunity to talk to patients about recommended vaccines during their frequent interactions

with patients, whether it be before, during, or after cancer therapy. This discussion

could result in better cancer care and ultimately save lives.”

Newest Trivalent Influenza Vaccine

Afluria is a mercury-free, purified, inactivated, trivalent influenza vaccine propagated in embryonic

chicken eggs. Each dose contains the required dose of influenza virus hemagglutinin

antigens from the influenza strains recommended and prioritized by the FDA’s Vaccine and Related

Biological Products Advisory Committee

for each flu season. Afluria was approved by

the FDA in September 2007 for the active immunization

of persons =18 years of age against

influenza disease caused by influenza subtypes

A and type B present in the vaccine.

Conclusion

The CDC recommend an annual flu shot for patients with cancer 50 years and older and

yearly pneumonia shots for patients older than 65 years. In a 2007 survey of people undergoing

radiation treatment for cancer, scientists found that among those who meet CDC

guidelines for annual vaccination, 25% have never had a flu shot and more than 30% had

never been vaccinated against pneumonia. Since patients with cancer have weakened

immune systems, they are especially susceptible to flu and pneumonia. Family members and

close contacts of these individuals also have an increased risk of infection and the CDC

advises them to make annual vaccinations a health priority.

References

1. Centers for Disease Control and Prevention. Prevention

and control of influenza. Recommendations of the Advisory

Committee on Immunization Practices (ACIP), 2008.

MMWR 2008;57:1-60.

2. Centers for Disease Control and Prevention. Update: Influenza

activity—United States and worldwide, 2006—2007

season, and composition of the 2007—2008 influenza

vaccine. MMWR 2007;56:789-794.

3. Thompson WW, Shay DK, Weintraub E, et al: Mortality associated

with influenza and respiratory synctyial virus in

the United States. JAMA 2003;289:179-186.

4. Thompson WW, Shay DK, Weintraub E, et al: Influenzaassociated

hospitalizations in the United States. JAMA

2004;292:1333-1340.

5. Barker WH, Mullooly JP: Impact of epidemic type A influenza

in a defined adult population. Am J Epidemiol

1980;112:798-811.

6. Neuzil KM, Wright PF, Mitchel EF, et al: The burden of influenza

illness in children with asthma and other chronic

medical conditions. J Pediatr 2000;137:856-864.

7. Centers for Disease Control and Prevention. Influenza

vaccine workgroup report. 2008. Available at: http://

www.cdc.gov/vaccines/recs/acip/downloads/mtgslides-

jun08/32-3-flu.pdf. Accessed August 9, 2008.

8. Centers for Disease Control and Prevention. Prevention

and control of influenza. Recommendations of the Advisory

Committee on Immunization Practices (ACIP), 2007.

MMWR 2007;56:1-54.

9. Yee S, Dutta P, Solin L, et al: Compliance with national vaccination

guidelines in patients receiving radiation therapy.

Int J Rad Onc Biol Physics 2007;69(suppl):S560.

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