4.5 Immunization of Children with Cancer
When using vaccines in immunosuppressed patients, one needs to be concerned about safety as well as efficacy. The following document contains guidelines for immunization of children with cancer both at the time of immunosuppressive therapy and following the end of their immunosuppressive therapy. They are based in part on existing guidelines or major reports wherever possible1-11. In general, all live virus vaccines should be avoided in the immunocompromised patient, and should not be given until at least three months following the end of immunosuppressive therapy. In the case of children receiving bone marrow transplantation, this period should be extended to at least 24 months (please see below for guidelines for immunization post-bone marrow transplantation).
In the cases of the non-live vaccines, the major concern is not safety, but rather efficacy. Thus, in general, it is advisable to give even inactivated vaccines at times of maintenance chemotherapy rather than during periods of intensive treatment as the antibody responses are likely to be better.
Considerations For Specific Vaccines
Vaccines That Are Contraindicated
In cancer patients, the possibility of complications from live vaccines is well recognized12-14. The oral polio (which is not recommended in Canada); yellow fever and oral typhoid vaccines are live and are contraindicated in the cancer patient. The live attenuated intranasal influenza vaccine is also contraindicated.
Measles, Mumps and Rubella:
Measles, mumps and rubella vaccines are relatively contraindicated, with the provisos as discussed above.
The varicella vaccine is also relatively contraindicated and is not approved for use in children with cancer. While accumulating data15-17 has resulted in recommendations from the American Academy of Pediatrics that suggests that immunization should be considered in susceptible children who have been in continuous remission from Acute Lymphoblastic Leukemia for at least 1 year, this should not be considered routine and should be done only in discussion with the patient’s tertiary centre. Two doses of vaccine are required to be considered immune.
Vaccines That Are Not Contraindicated
As indicated above, the non-live vaccines are not contraindicated in the cancer patient. Recommendations are based on limited data, expert opinion and consensus7, 8, 18-23. Table 1 summarizes these vaccines and specific relevant issues.
Diphtheria, Tetanus, Acellular Pertussis / Inactivated Polio/ Haemophilus Influenzae Type B Vaccine
Children with cancer should receive Hib-containing vaccine (such as Pediacel ®) according to routine vaccination schedules. Individuals (5 years of age and older) should receive one dose of Hib vaccine, regardless of prior history of Hib vaccination, and at least 1 year after any previous dose.
Children with Hodgkin’s disease are known to be at high-risk of invasive pneumococcal disease24-26. Those with other hematologic malignancies are presumed to be at high-risk of invasive pneumococcal disease and they require an alternative treatment schedule. There is a paucity of data on the use of the conjugate pneumococcal vaccine in immunosuppressed patients. Infants and children < 2 years of age should receive the regular childhood schedule for the conjugate vaccine. For previously unvaccinated children 24-59 months of age, most experts recommend 2 doses of the 13 valent conjugate vaccine 8 weeks apart followed 8 weeks later by a dose of the 23-valent pneumococcal vaccine. The 23-valent vaccine is not effective in children less than 24 months of age.
Children with cancer or those who are either asplenic, functionally asplenic, or one can anticipate a probability of needing splenectomy should receive the appropriate schedule of 13-valent conjugate vaccine followed 8 weeks later by the 23-valent polysaccharide vaccine.
Theoretically, cancer patients are at increased risk of meningococcal disease. Patients with Hodgkin’s disease are known to be at increased risk for serious bacterial infections with encapsulated organisms24-26. Conjugated vaccine is better than polysaccharide vaccine and should always be the product of choice in immunocompromised patients..
All Canadian provinces have universal, provincially funded programs, with somewhat different schedules. In Ontario, currently all infants are offered one conjugate meningococcal C vaccine dose at age 12 months. A quadrivalent (ACYW135) vaccine is offered to 12 year olds. For patients who are asplenic, functionally asplenic, or one can anticipate a probability of needing splenectomy should have conjugate quadrivalent vaccine. If under age two the vaccine should be Menveo, and any quadrivalent conjugate meningococcal ACYW135 (Menveo, Menactra, Nimenrix) if over age two. The use of conjugate quadrivalent meningococcal vaccine should replace the polysaccharide vaccine (Menomune) in all patients. Conjugate quadrivalent meningococcal vaccine is required every 5 years.
All people with asplenia or hyposplenism should receive quadrivalent conjugate meningococcal vaccine (Men-C-ACYW-135). The schedule for those who are previously unimmunized is as follows:
- Children aged 2 to 11 months should receive 2 or 3 doses of Menveo™ given 8 weeks apart (with another dose given between 12 to 23 months of age and at least 8 weeks from the previous dose) and booster doses as outlined below.
- Children aged 12 to 23 months should receive 2 doses of Menveo™ vaccine given at least 8 weeks apart and booster doses as outlined below.
- People aged 2 to 55 years should receive 2 doses of a Men-C-ACYW-135 vaccine (either Menactra®, Menveo, Nimenrix™) 8 weeks apart and booster doses as outlined below.
- Adults aged 56 years and over should receive 2 doses of a Men-C-ACYW-135 vaccine (either Menactra® ,Menveo™, Nimenrix) 8 weeks apart and booster doses as outlined below. If only one dose of Men-C-ACYW-135 vaccine was previously given, give another dose at the earliest opportunity and proceed with booster doses as outlined based on the interval from the second dose.
A booster dose of Men-C-ACYW-135 vaccine should be given every 5 years.
Killed Influenza Vaccines
Immunocompromised patients are at risk of adverse outcomes from influenza infections. Such patients, including those with cancer are candidates for the killed influenza vaccines yearly during the autumn season. Children receiving immunosuppressive chemotherapeutic agents may have less of an immune response compared with healthy children. Current recommendations suggest that the optimal timing of influenza vaccination is > 3 weeks after discontinuation of chemotherapy, or in maintenance and when the granulocyte and lymphocytes counts are 1.0 x 109/L or greater7. In practice, these conditions may be difficult to obtain, but vaccination should still be done. Ensure the child gets two doses, 4 weeks apart, if they have never before received influenza vaccination. Everyone they live with should also get influenza vaccination.
Travel-related Vaccination (Including Hepatitis A and B)
Travel is a good opportunity for health care providers to review and update the immunization status of children and those with whom they travel. The hepatitis A and B vaccines as well as the injectable typhoid vaccine should be considered if patients are visiting resource poor regions. Children with cancer should be fully vaccinated with hepatitis B vaccine, and have demonstrated protective titres. Hepatitis A vaccine is recommended if they are going to any resource poor country. Due to the incubation period of hepatitis A, the vaccine might be effective even if it is administered on the day of departure (as a last resort).
In addition to the above, cancer patients are candidates for hepatitis A and B vaccines if they have similar risk factors as healthy children (e.g., high-risk households, chronic liver disease, etc).
Varicella and Measles Exposures
Varicella / Zoster
While the varicella vaccine is relatively contraindicated in cancer patients, their siblings and susceptible household members should be vaccinated. In this regard, there is a small risk of transmission of vaccine virus from siblings to the cancer patient. However, the disease that is associated with vaccine virus tends to be mild, while the risk associated with natural varicella virus is more significant.
Cancer patients without a history of varicella or two confirmed doses of varicella vaccine should receive post-exposure prophylaxis with varicella zoster immune globulin (VariZIG) or acyclovir (if the VariZIG window is missed) 7, 29. Please refer to the POGO guideline on varicella exposure and use of VariZIG.
Pending additional data, if a patient has received immune globulin or blood products, it is recommended that the varicella vaccine be withheld. Immune globulin should not be administered within 2 weeks after measles or varicella vaccines are given. See: (http://www.phac-aspc.gc.ca/publicat/cig-gci/p01-10-eng.php#tabl).
The consequences of measles can be devastating for immunocompromised patients30. Cancer patients who have been exposed to measles should receive immune globulin (IG) 0.5 mL/kg IM (maximum 15 mL) as soon as possible. It is most effective within 3 days, but can be given up to 6 days after exposure regardless of their immunization status. Current lots of IVIG are likely to contain enough measles antibodies to offer protection. Patients who regularly receive IVIG (100 to 400 mg/kg) do not need additional prophylaxis if their last dose of IVIG was within 21 days of exposure to measles.
The use of immune globulin does alter the effectiveness of the measles vaccine if it is administered in close proximity to the dose of immune globulin. Please refer to the NACI table for the suggested intervals between the administration of such vaccines and receipt of immune globulin and other blood products http://www.phac-aspc.gc.ca/publicat/cig-gci/p01-10-eng.php – tabl. It is unknown if the same approach applies to the varicella vaccine. Pending additional data, if a patient has received immune globulin or blood products, it is recommended that the varicella vaccine be withheld for the same intervals as the measles vaccine. Immune globulin should not be administered within 2 weeks after measles or varicella vaccines are given.
Household and Healthcare Members
It is important for clinicians to be acutely aware that the vaccination of siblings and family members is an important strategy in the prevention of vaccine-preventable diseases in immunosuppressed patients. Family members need to ensure that their immunizations are up to date. Yearly influenza vaccination of family members is important in minimizing the potential for exposure to influenza within the home.
The role of varicella vaccine for family members is discussed above. The MMR vaccine can be safely administered to siblings and family members. While inactivated polio vaccine can be safely administered to family members, the oral polio vaccine (OPV) should not be administered. If OPV is inadvertently given to a household member, close contact between the immunocompromised patient and the OPV recipient should be minimized or avoided for 4-6 weeks. Oral polio vaccine is no longer available in Canada. Immunocompetent family members of immunosuppressed individuals can receive the live-attenuated yellow fever vaccine. There are no data to suggest that the use of the oral typhoid vaccine Ty21a in immunocompetent family members poses a risk of transmission to immunocompromised household members. Indeed, the concerns regarding the use of the vaccine in immunocompromised persons are theoretical and are not based on any case of disseminated vaccine-associated disease.
Health care workers who care for immuncompromised patients need to ensure that their immunizations are up to date. In this context, while all recommended vaccines are important, special attention to varicella, influenza, pertussis and hepatitis B vaccines is required.
Vaccination of Immunocompromised Persons with Acquired (Secondary) Immunodeficiency http://www.phac-aspc.gc.ca/publicat/cig-gci/p03-07-eng.php#a4
Ontario’s Publicly Funded Immunization Schedules
- Ambrosino DM, Molrine DC: Critical appraisal of immunization strategies for prevention of infection in the compromised host. Hematology – Oncology Clinics of North America 1993 Oct; 7(5):1027-1050.
- Hibberd PL, Rubin RH: Approach to immunization in the immunosuppressed host. Infectious Disease Clinics of North America 1990 Mar; 4(1):123-142.
- Ridgeway D, Wolff LJ: Active immunization of children with leukemia and other malignancies. Leukemia & Lymphoma 1993 Feb; 9(3):177-192.
- Anonymous. Recommendations of the Advisory Committee on Immunization Practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. Morbidity & Mortality Weekly Report. Recommendations & Reports 1993 Apr 9; 42(RR-4):1-18.
- Sung L, Heurter H, Zokvic KM. et al: Practical Vaccination Guidelines for Children with Cancer. Pediatric & Child Health 2001 July/Aug; 6(6):379-383.
- Centers for Disease Control and Prevention. Infectious Disease Society of America. American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among Hematopoietic Stem Cell Transplant recipients. Morbidity & Mortality Weekly Report. Recommendations & Reports 2000 Oct; 49(RR-10):1-125, CE1-7.
- American Academy of Pediatrics. In: Pickering LK, Baker CJ, Long SS, McMillan JA. eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics.
- National Advisory Committee on Immunization, Health Canada. Canadian Immunization Guide 7th edition 2006. Retrieved 2006 from www.naci.gc.ca.
- Somerville H: Immunisation recommendations following treatment of cancer. Australian Family Physician 2003 Jan/Feb; 32(1-2):33-34.
- Mahajan A, English MW, Jenney ME, Foot A: Survey of immunisation practices in the United Kingdom during and following completion of anti-cancer chemotherapy in children. Medical & Pediatric Oncology 2003 Apr; 40(4):270-271.
- Nilsson A, De Milito A, Engstrom P, Nordin M, Narita M, Grillner L, Chiodi F, Bjork, O: Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens. Pediatrics 2002 June; 109(6):e91. Retrieved 2006 from http://pediatrics.aappublications.org/cgi/content/full/109/6/e91.
- Geiger R, Fink FM, Solder B, Sailer M, Enders G: Persistent rubella infection after erroneous vaccination in an immunocompromised patient with acute lymphoblastic leukemia in remission. Journal of Medical Virology 1995 Dec; 47(4):442-444.
- Mitus AA, Holoway A, Evans AE, Enders JF: Attenuated measles vaccine in children with acute leukemia. American Journal of Diseases of Children 1962 Mar; 103:413-418.
- Pirofski LA, Casadevall A: Use of licensed vaccines for active immunization of the immunocompromised host. Clinical Microbioloy Reviews 1998 Jan; 11(1):1-26.
- Larussa P, Steinberg S, Gershorn AA: Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada. Journal of Infectious Diseases. 174 Suppl 3 1996 Nov; S320-323.
- Yeung CY, Liang DC: Varicella vaccine in children with acute lymphoblastic leukemia and non-Hodgkins lymphoma. Pediatric Hematology & Oncology 1992 Jan-Mar; 9(1):29-34.
- Gershon AA, Steinberg SP: Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine. New England Journal of Medicine 1989 Apr 6; 320(14):892-897.
- Nordey T, Aaberge IS, Husebekk A, Samdal HH, Steinert S, Melby H, Kolstad A: Cancer patients undergoing chemotherapy show adequate serological response to vaccinations against influenza virus and streptococcus pneumoniae. Medical Oncology 2002; 19(2):71-78.
- Shenep JL, Feldman S, Gigliotti F, Roberson PK, Marina N, Foreschle JE, Fullen GH, Lott L, Brodkey TO: Response of immunocompromised children with solid tumors to a conjugate vaccine for Haemophilus influenzae type b. Journal of Pediatrics 1994 Oct; 125(4):581-584.
- Molrine DC, George S, Tarbell N, Mauch P, Diller L, Neuberg D, Shamberger RC, Anderson EL, Phillips NR, Kinsella K: Antibody responses to polysaccharide and polysaccharide-conjugate vaccines after treatment of Hodgkin disease. Annals of Internal Medicine 1995 Dec 1; 123(11):828-834.
- Ercan TE, Soycan LY, Apak H, Celkan T, Ozkan A, Akdenizli E, Kasapcopur O, Yildiz I: Antibody titres and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology 2005 May; 27(5):273-277.
- Porter CC, Poehling KA, Hamilton R, Frangoul H, Cooper WO: Influenza immunization practices among pediatric oncologists. Journal of Pediatric Hematology/Oncology 2003 Feb; 25(2):134-138.
- Marec-Berard P, Floret D, Schell M, Mialou V, Frappaz D, Philip T, Bergeron C: Immunization for children treated for solid tumors: What are the guidelines? Archives de Pediatrie 2001 Jul; 8(7):734-743.
- Chilcote RR, Baehner RL, Hammond D: Septicemia and meningitis in children splenectomized for Hodgkin’s disease. New England Journal of Medicine 1976 Oct 7; 295(15):798-800.
- Donaldson SS, Glatstein E, Vosti KL : Bacterial infections in pediatric Hodgkin’s disease: relationship to radiotherapy, chemotherapy and splenectomy. Cancer 1978 May; 41(5):1949-1958.
- Landesman SH, Schiffman G: Assessment of the antibody response to pneumococcal vaccine in high risk populations. Reviews of Infectious Diseases 1981 Mar-Apr; 3 Suppl: S184-197.
- Public Health Agency of Canada, National Advisory Committee on Immunization (NACI). Update on meningococcal C conjugate vaccines. Canada Communicable Disease Report 2005 Apr 15; 31(ACS-3):1-4. Retrieved on September 6, 2006 from http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/05vol31/asc-dcc-3/index.html.
- Infectious Diseases and Immunization Committee, Canadian Pediatric Society. Meningococcal vaccine for children and adolescents. Paediatrics & Child Health 2005; 10(7):405-406. Retrieved September 2006 from http://www.cps.ca/English/statements/ID/ID05-01.htm
- Ishida Y, Tauchi H, Higaki A, Yokota-Outou Y, Kida K: Postexposure prophylaxis of varicella in children with leukemia by oral acyclovir. Pediatrics 1996 Jan; 97(1):150-151.
- Weitzman WS, Manson D, Wilson G, Allen U: Fever and respiratory distress in an 8 year old boy on therapy for acute lymphoblastic leukemia (ALL). Journal of Pediatrics 2003 Jun; 142(6):714-721.
- Ministry of Health and Long-Term Care, Ontario. Publicly funded immunization schedules for Ontario – October 2015. Retrieved November 17, 2015 from http://www.health.gov.on.ca/en/pro/programs/immunization/docs/immunization_schedule.pdf
Primary author Dr. Marina Salvadori, Children’s Hospital, London Health Sciences Centre, London with input from Dr. Nisha Thampi, Children’s Hospital, London Health Sciences Centre, London.