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Human Vaccines & Immunotherapeutics 11:11, 2606--2614; November 2015; 2015 Taylor & Francis Group, LLC
Treatment regimens for oncological diseases have evolved dra- Vaccine efficacy
matically over the past years and continue to change with the Vaccine efficacy, which is based on the reduction of infection
advent of new medications. Clinicians have become increasingly rates in a community, can be very difficult to assess in oncological
aware of the risk of infection associated with the malignancy itself patients owing to a low incidence of infection (e.g., tetanus) or
and/or immunosuppressive therapies, including higher risk for the seasonality of infection (e.g., influenza).10 Most data on vac-
pneumococcus, influenza infection and hepatitis B among cination in cancer patients are from underpowered studies that
others.1-4 In general, adults with oncological diseases should be include patients with different cancers and chemotherapy treat-
advised to adhere to standard recommended immunization sched- ments and that use diverse definitions of vaccine response.6
ules, but they should avoid live vaccines while on immunosuppres- Classically, vaccine response is measured by assessing pre- and
sive therapy. Types of immunizations are review in Table 1. post-vaccination antibody titers (Immunoglobulin G), which
The aim of this manuscript is to review the current evidence should be performed by the same laboratory. The precise meth-
and to elucidate the practical aspects of vaccination in patients ods used to measure vaccine response vary depending on the vac-
with oncological condition (excluding stem cell transplant recipi- cine as well as the antibody titer cut-off level used to indicate
ents) and family members, providing useful immunization rec- protection.11
ommendations for primary care providers, infectious diseases
practitioners and oncologists.
Inactivated Vaccines
Inactivated vaccines
In general, inactivated vaccines should be given at least 2 Influenza vaccine
weeks before the initiation of chemotherapy or other immuno- Cancer patients are known to be at great risk for morbidity
suppressive therapy to maximize the immune response. secondary to influenza infection, including bacterial pneumonia
and respiratory insufficiency,12-14 and mortality, the rate of
*Correspondence to: Ella J Ariza-Heredia; Email: eariza@mdanderson.org which ranges from 9% to 33% depending on the underlying
Submitted: 04/16/2015; Revised: 05/28/2015; Accepted: 06/10/2015
http://dx.doi.org/10.1080/21645515.2015.1062189 malignancy.13 Therefore, influenza vaccination should be
offered to all cancer patients except those receiving intensive
Non-replicating Based on toxoid, protein subunits, Tetanus, diphtheria, pertussis, poliomyelitis, Usually requires 35 doses; antibody titers
vaccines bacterial, antigens, or immunogenic hepatitis B, inuenza, Haemophilus diminishes with time
proteins obtained with recombinant, inuenza, pneumococcus, meningococcus
technology.
Replicating live Produced by disabling the virulent Measles-mumps-rubella, varicella, intranasal Severe reactions are possible;
attenuated vaccines properties of a disease-producing virus inuenza, yellow fever, oral polio, oral transmission of live pathogen may
or bacterium typhoid occur; most provide immunity with 1
dose
Passive immunization Antibodies are infused to provide short- Varicella Immunoglobulin, hepatitis B Protection diminishes after weeks or
term protection immunoglobulin months
chemotherapy (e.g., acute leukemia patients receiving induction Safdar et al. compared adult non-Hodgkin lymphoma patients
or consolidation therapy) or anti-B-cell antibodies. Family who received a 45-mcg-influenza vaccine with those who received
members and other close contacts of patients with cancer a 135-mcg vaccine and reported response rates of 40% and 60%,
should also be vaccinated against influenza.5 The recommended respectively; however, the study population was too small to
influenza vaccine in patients with cancer is the intramuscular determine whether this difference was statistically significant.24
inactivated vaccine. Intranasal administered live attenuated The authors also reported no difference in adverse reactions
influenza vaccine (LAIV) is currently not recommended for between the regular-dose and high-dose groups,24 although
patients with cancer as there is scarce data on safety. To our others have reported that the high-dose vaccine is associated with
knowledge, only one study by Carr et al.15 has evaluated the increased local pain and myalgia.25 The second novel method of
safety of LAIV in non-neutropenic children with cancer who delivering the influenza vaccine is the 2-shot influenza vaccine.
were classify as mild to moderately immunocompromised, Lo et al. found that the vaccine response rate of patients who
describing the live vaccine to be safe and immunogenic. How- received 2 doses (71%) was significantly higher than that of
ever as there is a safe non-live vaccine alternative, the current patients who received one dose (42%; p D 0.006).26 In another
recommendations including ours are to avoid LAIV. study, Cheng et al. reported sero-protection rates of 58.3% after
The timing of influenza vaccination in relation to chemother- one dose and 100% after 2 doses among children who had com-
apy helps to determine the vaccines serological response. Influ- pleted chemotherapy or who were receiving maintenance chemo-
enza is a seasonal disease, and waiting to give the vaccine until a therapy.27 One of the caveats of the 2-dose vaccination strategy is
few months after chemotherapy may not be an option in some the compliance rate, which for healthy children is 9.1%60.1%
clinical circumstances. For patients who are undergoing or who depending on age; adolescents tend to have lower compliance
are about to undergo chemotherapy, the best option may be to rates.28,29
administer the vaccine 2 weeks before or 2 weeks after chemo- Several aspects, including the seasonality and variation of
therapy or to administer the vaccine between chemotherapy influenza strains as well as difficulty achieving adequate statistical
cycles, and trying to avoid giving the vaccine when the patients power to identify significant differences between groups, limit
white blood cell counts are at their nadir.16 The concurrent researchers ability to accurately assess the effectiveness of the
administration of granulocyte-macrophage colony-stimulating influenza vaccine. However, a recent meta-analysis described that
factor at the time of vaccination is not recommended, as it was the rates of lower respiratory disease, hospitalization, and mortal-
not found to have a positive effect on the serological response to ity among cancer patients who received the influenza vaccine
influenza vaccination.17 were significantly lower than those among cancer patients who
The efficacy of the influenza vaccine is typically assessed by did not.30 Given this favorable risk-benefit profile, physicians
measuring hemagglutinin antibody titers. A serum antibody titer should make every effort to further increase the rate of influenza
of 40 or a 4-fold increase in the hemagglutinin titer is normally vaccination.
considered protective in healthy individuals.18 Using these
parameters, several studies have shown that the vaccine response Pneumococcal vaccine
varies depending on the cancer type. For instance, patients with Streptococcus pneumoniae infection may have serious implica-
breast cancer19,20 or lung cancer21 have mean vaccine response tions in patients with cancer including a high risk for invasive
rates of 66% and 78%, respectively, which are similar to that of pneumococcal disease especially for patients with multiple
the general population. On the other hand, patients with hema- myeloma, lung cancer, chronic lymphocytic leukemia, and
tological malignancies such as multiple myeloma have much lymphoma.31,32 However, owing to the low incidence of pneu-
lower vaccine response rates, which range from 19% to 27%.22,23 mococcal infection among cancer patients, documenting the
To improve the immunogenicity of influenza vaccination, effect of the pneumococcal vaccine in terms of reducing the
researchers have developed new methods of delivering the vac- risk for invasive pneumococcal disease is very difficult. Studies
cine, although none has become the standard of care. The first have suggested that the pneumococcal vaccine reduces the bur-
such method is the use of a high-dose vaccine. In one study, den of invasive pneumococcal disease and non-bacteremic
Inuenza Seasonal Administration of indicated inactivated vaccines 2 or Severe allergic reaction (e.g., anaphylaxis) after
more weeks prior to chemotherapy is preferred. previous dose of any inuenza vaccine; or to a
vaccine component, including egg protein
Pneumococcus Recommended Table 2 Severe allergic reaction (e.g., anaphylaxis) after a
previous dose or to a vaccine component,
including to any vaccine containing diphtheria
toxin
Td/Tdap Booster Replace a Td booster for Tdap An immediate anaphylactic reaction. Encephalopathy
occurring within 7 days following DTP vaccination
Hepatitis B 3 doses at 0,1 and 6 months All patients should be screened for immunity, and History of hypersensitivity to yeast or any vaccine
vaccinated as needed. Consider antibody component
measurement after last vaccine.
Hib Recommended for If patient is unimmunized, a dose of Hib should be Some of the combined Hib vaccines, such Hiberix,
splenectomized patients. offered after chemotherapy ActHib might contain natural rubber latex, which
Others, usual may cause allergy in latex sensitive persons.
recommendations
Meningococcus Splenectomized patients. For international travelers, vaccination is Vaccination with MenACWY, MPSV4, or Hib-MenCY-TT
Others, usual recommended for those visiting the parts of sub- is contraindicated among persons known to have a
recommendations Saharan Africa known as the meningitis belt severe allergic reaction to any component of the
during the dry season (DecemberJune). vaccine, including diphtheria or tetanus toxoid
Hepatitis A Usual recommendations Consider antibody testing in case of future exposure Contraindicated if history of previous allergy to the
(see text). after 2-3 years post-vaccination. vaccine or a component of the vaccine
MMR CAUTION May be considered in specic cases at least 3-6 Contraindicated while on chemotherapy or
months after chemotherapy (i.e. children not radiotherapy
vaccinated or epidemiological situation).
Recommend checking antibody level prior.
Varicella/Zoster CAUTION May be considered in children not previously Contraindicated if given <4 weeks of starting
vaccinated, at least 3-6 months after chemotherapy chemotherapy .No data is available after
is nished (see text). There is no data for Zoster chemotherapy
vaccination after chemotherapy.
Abbreviations: Td/Tdap (Tetanus diphtheria/ Tetanus/diphtheria/acellular pertussis), DTP (diphtheria, tetanus, and pertussis), MMR (Measles, mumps and
rubella), Hib (Heamophilus b conjugated vaccine), Hiberix (GlaxoSmithKline, England), ActHib (Sano-Pasteur, France).
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