IMMUNIZATION IN CHILDREN WITH CANCER

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SIOP PODC Supportive Care Education Presentation Date: 05 th September 2014 Recording Link at www.cure4kids.org: http://www.cure4kids.org/ums/home/conference_rooms/enter.php?room=p2xokm5imdj Email: ahmed.naqvi@sickkids.ca IMMUNIZATION IN CHILDREN WITH CANCER Ahmed Naqvi SickKids, Toronto

Challenges of Vaccinating Immunocompromised Children Safety issues Immunogenecity Decreased vaccine efficacy Changing immune status Heterogenous patient group with variable immune deficits Increasing use of potent immunosuppressive regimens Pre-immunosuppression immunization Vaccination of contacts to reduce exposure of the immune-compromised child compliance

Basic Principles of Vaccinating Immunocompromised Children Determine immune status Carefully assess risks versus benefits Understand that inactivated vaccines are generally safe and play an important role Live vaccines are generally contraindicated Vaccinate contacts and healthcare workers Follow current vaccine recommendations Administer vaccines before immune-suppression when possible Consider antibody testing to evaluate vaccine response

Heterogeneity in Hematopoeitic Stem Cell Transplant (HSCT) Recipients Degree of functional immune deficit Recipient age Underlying disease Previous treatment Conditioning regimen Source of stem cells Degree of human leukocyte antigen (HLA) mismatch Graft-versus-host disease Concomitant infections Preexisting immunity in the donor and recipients

Timing of Live Vaccines After Steroid Therapy and Chemotherapy Therapy Immuno ablative therapy AAP Red Book United Kingdom Australia Canada Steroid dose Topical (skin or respiratory tract) Local injection Physiologic Systemic steroids (low or moderate dose) Systemic steroids (high dose) for <2 weeks Systemic steroids (high dose) for 2 weeks Duration of Delay At least 3 months 6 12 months 12 months 12 months None None None None 2 weeks 1 month

Vaccine During chemotherapy After chemotherapy Level of evidence recommendation Level of evidence recommendation Poliomyelitis C III Benefit of herd immunity Postpone if lymphocyte count <1.0 X 10 9 /L B II Booster or vaccination 6 months after stopping chemotherapy Diphteria and Pertussis C III Postpone if lymphocyte count <1.0 X 10 9 /L Passive immunoprophylaxis and antibiotic prophylaxis in case of epidemic B II Booster or vaccination 6 months after stopping chemotherapy ( for diphteria adult type vaccine for age >6 years) Tetanus C III Postpone if lymphocyte count <1.0 X 10 9 /L Passive immunoprophylaxis, thorough hand washing and disinfection of wound and antobiotic therapy for wounds at risk. B II Booster or vaccination 6 months after stopping chemotherapy

Vaccine During chemotherapy After chemotherapy Level of evidence recommendation Level of evidence recommendation Hepatitis A virus C III Vaccination of seronegative patients before starting chemotherapy in highly endemic areas; alternatively passive immuneprophylaxis C III Booster or vaccination 6 months after stopping chemotherapy Hepatitis B virus B II As above B II Booster or vaccination 6 months after stopping chemotherapy Measles, Mumps, Rubella C III Not administered <12 months Passive immuneprophylaxis in case of contact Vaccination of seronegative family members B II Booster or vaccination 6 months after stopping chemotherapy

Vaccine During chemotherapy After chemotherapy Level of evidence recommendation Level of evidence recommendation Influenza B II Vaccination yearly during fall; Postpone if lymphocyte count <1.0 X 10 9 /L Vaccination of family members Not administered to infants <6 months of age Meningococcus C III Recommended prior to splenectomy Postpone if lymphocyte count <1.0 X 10 9 /L Not recommended if age <2 years B II Not recommeneded if age <2 years Booster or vaccination 6 months after stopping chemotherapy Booster after 3 years if vaccinated at age 2-6 years

Vaccine During chemotherapy After chemotherapy Level of evidence recommendation Level of evidence recommendation Hemophilus Influenzae C III Not administered if age <2 months Recommended prior to splenectomy Postpone if lymphocyte count <1.0 X 10 9 /L Pneumo-coccus C II Recommended prior to splenectomy Postpone if lymphocyte count <1.0 X 10 9 /L B II Not administered if age <2 months Booster or vaccination 6 months after stopping chemotherapy B II Booster or vaccination 6 months after stopping chemotherapy Varicella C II Vaccination of family members at risk Post exposure prophylaxis within 96 hours from contact B II Not administered if age <12 months Booster or vaccination 6 months after stopping chemotherapy

Contraindicated Vaccines in Immunosuppressed Children With Cancer and Hematopoeitic Stem Cell Transplant (HSCT) recipients Vaccine type Live bacteria Live virus Contraindicated Vaccines BCG, Ty21a Salmonella typhi LAIV, MMR, varicella, OPV, yellow fever, rotavirus (RV1, RV5)

Live Viral Vaccines: Oral Poliovirus Vaccine (OPV) Contraindicated in patients and their household contacts because of the risk of vaccine-associated polio in immunocompromised children Viral shedding may occur in OPV recipients for 8 12 weeks after vaccine administration. If OPV is introduced into the household of an immunocompromised child, the vaccinee should practice proper hand hygiene

Live Viral Vaccines: Varicella Vaccine Immunosuppressed patients are at a high risk of complications from varicella infection Should not be routinely administered to children who have T- lymphocyte immunodeficiency, including those with leukemia, lymphoma, and other malignant neoplasms affecting the bone marrow Patients who have received high dose steroids for 14 days should not receive varicella vaccine at least for a month The timing of vaccine administration is controversial Patient in continuous remission for at least one year with lymphocyte counts of >0.7 x 10 9 /L and platelet counts of >100 x 10 9 /L

Live Viral Vaccines: MMR Vaccine Should be withheld for at least 3 months after therapy is completed Already immunized should receive a booster dose 6 months after therapy is completed Immune response 3-6 months after the completion of chemotherapy is similar to age matched healthy children Exposure to measles in unimmunized child Ig should be given Revaccination after HSCT should be delayed for at least 24 months who are no longer on immune suppression and do not have GVHD.

Live Virus Vaccines: Rotavirus Vaccine Contraindicated in patients with SCIDS Unproven safety in infants with immune deficiency

Recommendations for household contacts and health-care personnel All routine age-specific vaccines be given according to the local immunization schedules Administer MMR to all children aged 12 months who are likely to come in contact Administer inactivated influenza vaccine annually to all household members more than 6 months of age Immunize all contacts at risk for chicken pox with varicella vaccine. Transmission of infection after vaccination can occur rarely. If vaccine recipient develops a rash, should avoid contact with patient. In case of any symptoms of varicella in patient, consider acyclovir.

Recommendations for household contacts and health-care personnel Administer all household contacts with Rota virus vaccine All health care givers, who are non-immunized against tuberculosis, hepatitis B, Measles, Mumps, Rubella, Influenza, and varicella should be vaccinated for these diseases Pregnant women can safely receive adult-type tetanus and Diphtheria toxoid (Td), inativated influenza, pneumococcal, hepatitis A, and hepatitis B vaccines. All live vaccines including MMR, varicella, and live influenza are contraindicated