IMMUNIZATION OF THE CHILD WITH CANCER: ACTIVE IMMUNIZATION OF CHILDREN ON CHEMOTHERAPY

A. Bacterial immunization

1. Diphtheria, tetanus, acellular pertussis (DTaP) immunizations

a.     Few infections with these organisms are seen, probably

due to some protection from earlier immunizations

and herd immunity.

b.     Several studies report adequate responses to primary

and booster DTaP immunizations given during

chemotherapy.

c.     Children receiving more aggressive therapies may be

less likely to respond as well as those receiving standard therapies.

d.     Recommendations

i. Children on maintenance therapy should be given DTaP immunizations at scheduled times.

ii.     If therapy is short in duration or to be discontinued

shortly after the DTaP is due, then delay immunization until therapy is completed.

iii.     DTaP titers may fall during active therapy; there-

fore, a booster dose of DTaP for children < 7 yrs and

(diphtheria tetanus (DT) for children < 7 yrs of age)

is recommended at 1 year after the completion of

therapy.

2. Polysaccharide vaccines: pneumococcus, meningococcus, and Haemophilus influenzae type b Children receiving chemotherapy are at an increased risk of infection with polysaccharide-encapsulated pathogens, especially during the first 4 years of life. An increased incidence of pneumococcal and H. influenzae type b disease is seen in children with acute lymphoblastic leukemia (ALL) and in splenectomized patients with Hodgkin disease. Although less frequent, meningococcal disease has been reported in such patients.

a.     Several studies have documented an adequate

response to the pneumococcal polysaccharide and H.

influenzae vaccines in patients with acute leukemia,

Hodgkin disease, and solid tumors.

b.     Fifty to 85% of children with leukemia and 45% of children with solid tumors have a significant antibody response after receiving H influenzae type b diphtheria toxoid conjugate.

i.     The response is greatest in children immunized in

the first 12 months of therapy for leukemia, with

antibody levels declining during continued therapy.

ii.     In Hodgkin disease, the antibody response is only

minimally impaired if the vaccine is given more than

10 days before the initiation of therapy or beforesplenectomy. Responses to polysaccharide vaccines may not be normal for as long as 4 years after treatment.

c. Recommendations

i.     The Centers for Disease Control and Prevention

(CDC) recommends immunization with pneumococcal, meningococcal, and H. influenzae type b

conjugate vaccines for all immune-compromised

patients. However, few data support vaccination for

pneumococcus and meningococcus in children

receiving chemotherapy.

ii.     Unvaccinated children with ALL or solid tumors

should be vaccinated during maintenance therapy

per recommendations for age.

iii.     Patients with Hodgkin disease undergoing splenectomy or splenic radiation should be immunized at least

7-10 days before therapy begins and be given booster doses of pneumococcal and H. influenzae type b

vaccines 3-5 years after the completion of therapy.

iv.     Patients with surgical or functional asplenia (due to

radiation of the spleen) should be given meningococcal vaccine in the pretreatment period and then

a booster 2-3 years later. After this period of time,

boosters for pneumococcus and meningococcus

should be given every 5-6 years, as recommended

for high-risk adults. For ALL and solid tumor

patients receiving H. influenzae type b during therapy, a booster should be given 1 year after the completion of therapy.

B. Viral immunization

1. Measles, mumps, rubella (MMR)

a. The safety of this vaccine in immune-compromised hosts has been a concern since the death of a patient ho received it during therapy over 30 years ago! A further attenuated measle vaccine has been studied in a small study of leukemic children after cessation of therapy and was found to be safe. Several small studies, however, have found that, although the measles vaccine is relatively safe, patients have a suboptimal and short-lasting antibody response.

b. Recommendation

MMR is contraindicated for any child with cancer currently undergoing therapy. Reimmunization of all patients with MMR is recommended at 1 year after the completion of therapy, then every 10 years.

2.     Polio

a.     Do not give oral polio vaccine (OPV) to immune-com-

promised patients or their siblings, due to their

increased susceptibility to vaccine-associated polio.

b.     Inactivated killed polio vaccine (IPV) is an alternative

for immune-compromised patients, but may not be

adequate for primary immunization during therapy.

c.     Recommendations

i.     IPV can be substituted for booster doses at appropriate times for patients previously partially immunized.

ii.     For unimmunized children (or in areas in which

polio is endemic), IPV can be given for primary

immunization, but reimmunization with OPV 1 year

after the cessation of therapy is recommended.

iii.     Partially immunized children can receive either

OPV or IPV 1 year after cessation of therapy.

3.     Hepatitis B

a.     Children with cancer are at risk for blood-borne infections due to numerous procedures requiring venous

access and frequent transfusion of blood products.

Additionally, children with cancer have an increased

risk of becoming chronic hepatitis B surface antigen

(HBsAg) carriers.

b.     Children receiving chemotherapy have an impaired,

yet adequate, serologic response to hepatitis B vaccine

(HBV). The protective titer of antibody after three

doses of vaccine is achieved in up to 67% of children

receiving chemotherapy for solid tumors and hematologic malignancies, compared with 97% in children

with benign conditions.

c. Recommendation

The administration of HBV at 0-, 1-, and 6-month intervals is recommended for previously unimmunized children on therapy. Obtain titers after immunization to ascertain an adequate response.

4.     Influenza

a.     The safety of inactivated influenza vaccine in cancer

patients is well established, yet efficacy data are mini-

mal and controversial. Studies of vaccination in children with cancer on therapy found both a significant

impairment of antibody response while some demonstrate a protective antibody titer.

b.     Recommendation

The CDC recommends influenza vaccine for all children, on a yearly basis, during periods of active immune suppression (on therapy and up to 1 year after cessation of therapy). It is recognized that this is not the general practice due to incomplete data. For optimal immunogenicity, two doses should be given, 4 weeks apart. It is not necessary to interrupt chemotherapy. Influenza vaccine can safely be given to immune-compromised patients over the age of 6 months.

5.     Varicella vaccine

a.     Although safe and effective, the varicella vaccine has

not been licensed for use in children with malignancies, but may be used on a compassionate basis in children with leukemia. Eighty-five percent of children with

ALL during maintenance therapy have serologic evidence of an immune response after receiving one dose,

and more than 90% after two doses, independent of

whether chemotherapy is withheld or not.

b.     Immune-compromised children have a higher incidence of vaccine-associated varicella than healthy children (up to 40% versus <5%); however, the attack rate

is much lower than with exposure to wild-type varicella

and the vaccine-associated illness usually has an

extremely mild, often subclinical, course. Overall, the

vaccine is felt to be more than 80% effective in preventing clinical varicella in children with leukemia and

100% effective in preventing severe varicella in this

high-risk population. Current data indicate that this

immunity does not wane significantly with time.

c.     Additionally, the vaccine provides a protective effect

against zoster and, with a booster, reduces the risk

from 15% to a 3% risk.

d.     Recommendations

i.     Varicella vaccine is recommended for all susceptible children with ALL during maintenance, 12

months after documented remission. A first dose

confers immunity and a second dose given 3

months later boosts the antibody titer. Varicella

titers should be checked several months after the

second dose and then yearly to determine if a third

dose is necessary.

ii.     Therapy should be interrupted for 1 week before

and 1 week after the patient receives the first dose of

the vaccine and timed such that it not be given with-

in one week of the prednisone pulse. It is not necessary to interrupt therapy for the second injection.

iii.     The absolute lymphocyte count should be at least

700/uL at the time of vaccination.

iv.     Due to the possibility of rash-associated transmission of the virus to other immune-compromised children, vaccinated children should be examined to rule

out vaccine associated varicella before they come to

the oncology clinic for 4-5 weeks after the vaccine.

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Cancer