Abstract
Cancer survivors are at an elevated risk for infection because of immune suppression associated with prior cancer treatments, and they are at increased risk of complications from vaccine-preventable diseases. This section of the NCCN Guidelines for Survivorship provides recommendations for the prevention of infections in survivors through education, antimicrobial prophylaxis, and the judicious use of vaccines. These guidelines provide information about travel and gardening precautions and safe pet care/avoidance of zoonosis, and include detailed recommendations regarding vaccinations that should be considered and encouraged in cancer and transplant survivors.
Cancer survivors are at elevated risk for infection because of immune suppression associated with previous cancer treatments, such as chemotherapy, radiation, corticosteroids, certain surgeries, and stem cell transplantation. In fact, antibody titers to vaccine-preventable diseases decrease after anticancer treatment.1,2 In addition, survivors are at increased risk of complications from vaccine-preventable diseases, such as those caused by human papillomaviruses (HPV) and influenza viruses.2,3
Many infections in survivors can be prevented by the use of vaccines. However, a recent report of data from the Behavioral Risk Factor Surveillance System (BRFSS) found that 42% of survivors did not receive an influenza vaccination in 2009, and 52% reported never receiving a pneumococcal vaccination.4 Analysis of the SEER-Medicare database showed that breast cancer survivors, aged 65 years or older, were less likely to receive an influenza vaccination than matched noncancer controls.5 A separate analysis of the SEER-Medicare database by another group found similar results.6
Vaccines represent a unique challenge in cancer and transplant survivors because they may not trigger the desired protective immune responses because of possible residual immune deficits.7 In addition, certain vaccines, such as those that are live attenuated (eg, zoster; measles, mumps, rubella [MMR]), are contraindicated in actively immunosuppressed survivors because of an increased risk of developing the disease and/or prolonged shedding from the live organism given in the vaccine.
Risk Assessment and Screening for Immunizations and Prevention of Infections
Survivors are at elevated risk for infections if their cancer treatment included chemotherapy, monoclonal antibodies, radiation, corticosteroids, splenectomy, and/or hematopoietic cell transplantation (HCT; which includes peripheral blood stem cell transplantation, bone marrow transplantation, and cord blood transplantation). Risk is also elevated if the survivor has prior or current exposure to endemic infections or epidemics, or has a history of blood transfusion.
Interventions for Prevention of Infections
Infection in survivors can be prevented by education, antimicrobial prophylaxis, and the judicious use of vaccines.
Antimicrobial Prophylaxis and Education
Survivors should be educated about safe pet care/the avoidance of zoonosis, travel precautions, and gardening precautions.8–13 Safe pet care tips include washing hands with soap and running water after handling animals and their feces. If possible, survivors should avoid direct contact with animal feces. Travel precautions include education on the need for pretravel vaccines, prophylaxis against specific infections, and education on how to prevent waterborne, airborne, and zoonotic infections. Travelers may find useful information at http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-8-advising-travelers-with-specific-needs/immunocompromised-travelers or through consulting a travel clinic. Gardening precautions include wearing gloves to avoid cuts and punctures that could be delayed in healing or could become infected with fungus or staphylococcus/streptococcus that may be present on thorns, and wearing a protective mask to avoid inhalation of spores.
For information regarding antimicrobial prophylaxis, please see the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections (to view the most recent version of these guidelines, visit NCCN.org).
Immunizations
Vaccination, or “active immunization,” involves administration of all or part of a microorganism or a modified product of a microorganism (eg, a toxoid, a purified antigen, or an antigen produced by genetic engineering) to produce an immunologic response that mimics that of natural infection but usually presents little or no risk to the recipient. The use of vaccines that do not contain live organisms should be considered and encouraged in all cancer and transplant survivors who have completed therapy at least 3 months before the planned vaccine administration. In general, the usual doses and schedules are recommended, as outlined by the Advisory Committee on Immunization Practices.14,15 The Infectious Diseases Society of America has outlined guidance for vaccination in immunocompromised patients, including those with cancer and those post-HCT.16 The NCCN Survivorship Panel outlined immunization guidelines specific to survivors of hematologic malignancies and solid tumors, with separate guidelines for survivors who received HCT. In survivors who received anti–B-cell antibody therapy, vaccination should be delayed for at least 6 months after chemotherapy or the last dose of such therapy to allow for reconstitution of the B-cell population. More details are available in the guidelines (NCCN.org).
Before vaccination, immune system viability and history of allergic reactions to vaccines should be assessed. Baseline WBC counts should be in the normal range or within reasonable limits before starting vaccinations, unless they are elevated because of disease status. The survivor should not be on immunosuppressive drugs or chemotherapy, and ongoing infection should not be present.
The following vaccines should be considered and encouraged for all survivors, administered according to the usual doses and schedules: influenza vaccine (only inactivated or recombinant); pneumococcal vaccine (PPSV-23/PCV-13); tetanus, diphtheria, pertussis (Tdap); and HPV (in survivors aged ≤26 years).17–19 These vaccines do not contain live organisms; instead they contain inactivated organisms, purified antigens, bacterial components, or genetically engineered recombinant antigens. The effectiveness of these vaccinations might be suboptimal because of lingering immune suppression.7 However, in the absence of known harm, their administration may be worthwhile with the hope of achieving some protection.
Other vaccines, as listed in the guidelines, should be considered in consultation with an infectious disease or travel medicine specialist if unique circumstances in the survivor’s lifestyle, upcoming travel, or local epidemic/risks merit their use.
Influenza Vaccines
Annual influenza vaccination is recommended for all cancer and transplant survivors. Live attenuated influenza vaccines should generally be avoided in this population. Preferred vaccines include inactivated influenza vaccines (ie, trivalent [IIV3] standard-dose, trivalent [IIV3] high-dose, and quadrivalent [IIV4] standard-dose) or, for individuals with egg allergies, recombinant influenza vaccine (ie, trivalent [RIV3]).15,20 To date, no evidence shows superiority of any one of these vaccines.
Live Viral Vaccines
Vaccines that contain live attenuated organisms (eg, live-attenuated influenza vaccine; MMR; oral polio vaccine [OPV]) are contraindicated in actively immunocompromised survivors because of a proven or theoretical increased risk of disease and prolonged shedding from the live organism present in the vaccine. They should not be offered to actively immunocompromised survivors unless cleared by a clinician experienced in vaccine use or by an infectious disease specialist. However, live viral vaccines can be administered to immunocompetent survivors 3 or more months after treatment, but consultation with an infectious disease specialist or clinician familiar with vaccination in patients with cancer is recommended. An exception is the live-attenuated influenza vaccine, which should be avoided in survivors because safer alternatives exist (see earlier discussion).
Healthy immunocompetent individuals who live in a household with immunocompromised survivors can receive the following live vaccines: MMR, rotavirus vaccine in infants aged 2 to 7 months, varicella vaccine (VAR), and zoster vaccine. However, OPV should not be administered to individuals who live in a household with immunocompromised survivors. Highly immunocompromised survivors should avoid handling diapers of infants who have received the rotavirus vaccine for 4 weeks after vaccination. Immunocompromised survivors should avoid contact with persons who develop skin lesions after receipt of VAR or zoster vaccine until the lesions clear.
Zoster (Shingles) Vaccine
A single dose of zoster (shingles) vaccine is recommended for survivors aged 60 years or older without active or ongoing immunodeficiency, no history of cellular immunodeficiency or HCT, or who have not received chemotherapy or radiation within the past 3 months, and it can be given at least 4 weeks before initiation of chemotherapy or immunosuppressive drugs.16,21,22 Zoster vaccination should also be considered for survivors aged 50 to 59 years with a history of varicella or zoster infection (VZV) or VZV seropositivity with no previous doses of varicella vaccine. The zoster vaccine should be avoided in immunocompromised survivors, but can be considered in transplant survivors without active graft-versus-host disease or enhanced immunosuppression 24 or more months after transplantation.
NCCN Survivorship Panel Members
*,a,cCrystal S. Denlinger, MD/Chair†
Fox Chase Cancer Center
*,c,dJennifer A. Ligibel, MD/Vice Chair†
Dana-Farber/Brigham and Women’s Cancer Center
fMadhuri Are, MD£
Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center
b,eK. Scott Baker, MD, MS€ξ
Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
*,cWendy Demark-Wahnefried, PhD, RD≅
University of Alabama at Birmingham Comprehensive Cancer Center
*,b,d,g Don Dizon, MD†
Massachusetts General Hospital Cancer Center
b,dDebra L. Friedman, MD, MS€‡
Vanderbilt-Ingram Cancer Center
*,gMindy Goldman, MDΩ
UCSF Helen Diller Family Comprehensive Cancer Center
*,c,dLee Jones, PhDΠ
Memorial Sloan Kettering Cancer Center
bAllison King, MD€Ψ‡
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
eGrace H. Ku, MDξ‡
UC San Diego Moores Cancer Center
*,b,hElizabeth Kvale, MD£
University of Alabama at Birmingham Comprehensive Cancer Center
aTerry S. Langbaum, MAS¥
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
gKristin Leonardi-Warren, RN, ND#
University of Colorado Cancer Center
bMary S. McCabe, RN, BS, MS#
Memorial Sloan Kettering Cancer Center
b,c,d,gMichelle Melisko, MD†
UCSF Helen Diller Family Comprehensive Cancer Center
*,eJose G. Montoya, MDΦ
Stanford Cancer Institute
a,dKathi Mooney, RN, PhD#
Huntsman Cancer Institute at the University of Utah
c,eMary Ann Morgan, PhD, FNP-BC#
Moffitt Cancer Center
Javid J. Moslehi, MDλÞ
Vanderbilt-Ingram Cancer Center
d,hTracey O’Connor, MD†
Roswell Park Cancer Institute
cLinda Overholser, MD, MPHÞ
University of Colorado Cancer Center
cElectra D. Paskett, PhDε
The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
Jeffrey Peppercorn, MD, MPH†
Duke Cancer Institute
f,hMuhammad Raza, MD‡
St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center
M. Alma Rodriguez, MD‡
The University of Texas MD Anderson Cancer Center
*,fKaren L. Syrjala, PhDθ
Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
*,fSusan G. Urba, MD†£
University of Michigan Comprehensive Cancer Center
gMark T. Wakabayashi, MD, MPHΩ
City of Hope Comprehensive Cancer Center
*,hPhyllis Zee, MDΨΠ
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
NCCN Staff: Nicole R. McMillian, MS, and Deborah A. Freedman-Cass, PhD
KEY:
*Writing Committee Member
Subcommittees: aAnxiety and Depression; bCognitive Function; cExercise; dFatigue; eImmunizations and Infections; fPain; gSexual Function; hSleep Disorders
Specialties: ξBone Marrow Transplantation; λCardiology; εEpidemiology; ΠExercise/Physiology; ΩGynecology/Gynecologic Oncology; ‡Hematology/Hematology Oncology; ΦInfectious Diseases; ÞInternal Medicine; †Medical Oncology; ΨNeurology/Neuro-Oncology; #Nursing; ; ≅Nutrition Science/Dietician; ¥Patient Advocacy; €Pediatric Oncology; θPsychiatry, Psychology, Including Health Behavior; £Supportive Care Including Palliative, Pain Management, Pastoral Care, and Oncology Social Work; ¶Surgery/Surgical Oncology; ωUrology
Footnotes
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way. The full NCCN Guidelines for Survivor-ship are not printed in this issue of JNCCN but can be accessed online at NCCN.org.
© National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.
Disclosures for the NCCN Survivorship Panel
At the beginning of each NCCN Guidelines panel meeting, panel members review all potential conflicts of interest. NCCN, in keeping with its commitment to public transparency, publishes these disclosures for panel members, staff, and NCCN itself.
Individual disclosures for the NCCN Survivorship Panel members can be found on page 1111. (The most recent version of these guidelines and accompanying disclosures are available on the NCCN Web site at NCCN.org.)
These guidelines are also available on the Internet. For the latest update, visit NCCN.org.
| Panel Member | Clinical Research Support/Data Safety Monitoring Board | Advisory Boards, Speakers Bureau, Expert Witness, or Consultant | Patent, Equity, or Royalty | Other | Date Completed |
|---|---|---|---|---|---|
| Madhuri Are, MD | None | None | None | None | 5/15/13 |
| K. Scott Baker, MD, MS | None | None | None | None | 11/22/13 |
| Wendy Demark-Wahnefried, PhD, RD | National Cancer Institute; Harvest for Health Gardening Project for Breast Cancer Survivors; and Nutrigenomic Link between Alpha-Linolenic Acid and Aggressive Prostate Cancer | American Society of Clinical Oncology | None | American Society of Preventive Oncology | 11/13/13 |
| Crystal S. Denlinger, MD | Bayer HealthCare; ImClone Systems Incorporated; MedImmune Inc.; OncoMed Pharmaceuticals; Astex Pharmaceuticals; Merrimack Pharmaceuticals; and Pfizer Inc. | Eli Lilly and Company | None | None | 1/9/14 |
| Don Dizon, MD | None | None | None | American Journal of Clinical Oncology; ASCO; UpToDate | 4/4/14 |
| Debra L. Friedman, MD, MS | None | None | None | None | 5/26/13 |
| Mindy Goldman, MD | Pending | ||||
| Lee W. Jones, PhD | None | None | None | None | 2/2/12 |
| Allison King, MD | None | None | None | None | 8/12/13 |
| Grace H. Ku, MD | None | Seattle Genetics, Inc. | None | None | 5/6/14 |
| Elizabeth Kvale, MD | None | None | None | None | 10/7/13 |
| Terry S. Langbaum, MAS | None | None | None | None | 8/13/13 |
| Kristin Leonardi-Warren, RN, ND | None | None | None | None | 1/6/14 |
| Jennifer A. Ligibel, MD | None | None | None | None | 10/3/13 |
| Mary S. McCabe, RN, BS, MS | None | National Cancer Institute | None | None | 5/6/14 |
| Michelle Melisko, MD | Celldex Therapeutics; and Galena Biopharma | Agendia BV; Genentech, Inc.; and Novartis Pharmaceuticals Corporation | None | None | 10/11/13 |
| Jose G. Montoya, MD | None | None | None | None | 12/6/13 |
| Kathi Mooney, RN, PhD | University of Utah | None | None | None | 7/15/14 |
| Mary Ann Morgan, PhD, FNP-BC | None | None | None | None | 5/5/14 |
| Javid J. Moslehi, MD | None | ARIAD Pharmaceuticals, Inc.; Millennium Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer Inc. | None | None | 1/27/14 |
| Tracey O’Connor, MD | None | None | None | None | 6/13/13 |
| Linda Overholser, MD, MPH | None | Antigenics Inc.; and Colorado Central Cancer Registry Care Plan Project | None | None | 10/10/13 |
| Electra D. Paskett, PhD | Merck & Co., Inc. | None | Pfizer Inc. | None | 5/7/14 |
| Jeffrey Peppercorn, MD, MPH | Pending | ||||
| Muhammad Raza, MD | None | None | None | None | 8/23/12 |
| M. Alma Rodriguez, MD | Amgen Inc.; Ortho Biotech Products, L.P. | None | None | None | 4/4/14 |
| Karen L. Syrjala, PhD | None | None | None | None | 5/1/14 |
| Susan G. Urba, MD | None | Eisai Inc.; and Helsinn Therapeutics (U.S.), Inc. | None | None | 10/9/13 |
| Mark T. Wakabayashi, MD, MPH | None | None | None | None | 6/19/13 |
| Phyllis Zee, MD | Philips/Respironics | Merck & Co., Inc.; Jazz Pharmaceuticals; Vanda Pharmaceuticals; and Purdue Pharma LP | None | None | 3/26/14 |
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