Pediatric cancer survivors have increased infection-related morbidity and mortality. This study will evaluate immune dysfunction following cancer directed systemic therapy completion, with attention to clinical relevance and infection rate in this population compared to healthy siblings, when applicable. The investigators will also restart vaccinations at earlier time points than previously studied, at 3 months post therapy, and will assess whether boosters or revaccination schedules are superior for regaining immunity against potentially serious infections in survivors.

This study is a prospective, randomized trial. The target population is all patients between the ages of 2 and 21 years of age who complete cancer directed systemic therapy for any malignant diagnosis at our center over a 2 to 3-year time frame. The study will be conducted in the various disease-specific off therapy and survivorship clinics of Levine Children's Cancer and Blood Disorders. Patients will have lab evaluations for immune function at baseline, 3, 6, 12, and 24 months from last dose of cancer directed systemic therapy. At 3 months from last dose of cancer directed systemic therapy, patients with abnormal vaccine antibody titers will be randomized to receive either single booster vaccines or to begin a full revaccination series that models post-hematopoietic stem cell transplant vaccination strategies. Vaccines given will be directed against Haemophilus influenza type B, tetanus, diphtheria, pertussis, polio, hepatitis B, Streptococcus pneumoniae, measles, mumps, rubella, and varicella. Live vaccines (measles, mumps, rubella, and varicella) will be given at 6 months from last dose of cancer directed systemic therapy. Repeat vaccine antibody titers will be assessed at follow up visits as above to determine if there are differences in immediate or maintained immunity based on vaccine strategy used. For subjects <18 years of age, we will present health questionnaires to their caregiver to answer at each of the time points. Subjects ≥18 years of age will complete their own health questionnaire. These questionnaires will assess frequency, type, and severity of viral and bacterial infections requiring antibiotics in study patients and their closest healthy sibling in age, when applicable.

Inclusion Criteria:

1. Written informed consent, HIPAA authorization for release of personal health information, and assent, when applicable from the subject, parent, or legal guardian.
2. Age greater than or equal to 2 years and less than 22 years at the time of consent
3. Lansky/Karnofsky Performance Status of greater than 50 (ECOG less than 2) within 30 days prior to date of enrollment
4. Histological or cytological confirmation of any malignancy treated by the Pediatric Oncology team of Levine Children's Hospital
5. History of any malignant diagnosis treated with at least one cycle of cancer directed systemic therapy
6. Must be no more than 60 days from last dose of cancer directed systemic therapy at time of enrollment
7. As determined by the enrolling physician, ability of the subject and parent/caregiver to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

1. Malignant disease treated with observation, surgery, or radiotherapy alone
2. Known coexisting immunodeficiency
3. Subjects with normal baseline titers for all investigated vaccines
4. Known pregnancy
5. Documented previous severe allergic reaction to any vaccine or component of a vaccine
6. Documented current/active, severe infection, as determined by the investigator