Overview
Definition:
Immunocompromised children, particularly those undergoing chemotherapy for malignancies or receiving immunosuppressive therapy for non-malignant conditions, have a significantly altered immune status, rendering them highly susceptible to vaccine-preventable diseases
Immunizations in this population require careful timing and selection of vaccine types to balance the risk of infection with the potential for reduced vaccine efficacy and increased risk of vaccine-related adverse events.
Epidemiology:
The incidence of infections in immunocompromised children is high, with vaccine-preventable diseases posing a significant threat
The use of chemotherapy agents like alkylating agents, antimetabolites, and anthracyclines profoundly impacts B and T cell function, leading to impaired humoral and cell-mediated immunity
The specific type of cancer, stage of treatment, and intensity of immunosuppression influence the degree of immunocompromise.
Clinical Significance:
Appropriate immunization strategies are crucial for preventing serious morbidity and mortality from infectious diseases in these vulnerable children
Failure to vaccinate or incorrect timing can lead to life-threatening infections
Understanding the nuances of live attenuated versus inactivated vaccines, the impact of chemotherapy cycles, and the timing of revaccination is critical for pediatric oncologists, hematologists, and infectious disease specialists managing these patients.
General Principles
Assessing Immunocompromise:
Categorizing the degree of immunocompromise is essential
Factors include underlying condition (cancer, transplant, primary immunodeficiency), type and duration of immunosuppressive therapy (chemotherapy, corticosteroids, biologics), and absolute neutrophil count (ANC) and lymphocyte counts
Generally, children with an ANC < 500/mm³ or receiving intense immunosuppression are considered at high risk.
Live Attenuated Vaccines:
Live attenuated vaccines (e.g., MMR, Varicella, Rotavirus, BCG, Oral Polio) carry a theoretical risk of causing disseminated infection in severely immunocompromised individuals
Their use is generally contraindicated or requires extreme caution based on the specific level of immunosuppression and vaccine type
Recommendations vary by guidelines.
Inactivated Vaccines:
Inactivated vaccines (e.g., IPV, DTaP, Hib, PCV, Influenza, HepA/B) are generally considered safe for immunocompromised children
However, their immunogenicity may be reduced, necessitating higher doses, additional doses, or revaccination upon completion of immunosuppressive therapy.
Timing Considerations:
Vaccination should ideally occur when the child is least immunocompromised, such as before initiation of immunosuppressive therapy or during periods of immune recovery
Specific chemotherapy regimens and their myelosuppressive effects dictate the optimal timing
Post-chemotherapy revaccination is often recommended to achieve adequate immunity.
Vaccination Timing Around Chemotherapy
Before Chemotherapy:
Whenever possible, administer inactivated and live attenuated vaccines at least 2-4 weeks before initiating immunosuppressive therapy or chemotherapy
This allows for optimal immune response before immune function is compromised
For live vaccines, consider the specific risks and benefits in consultation with specialists.
During Chemotherapy:
Avoid live attenuated vaccines during periods of significant immunosuppression (e.g., ANC < 500/mm³, during intense induction chemotherapy, or within 4 weeks of receiving certain immunosuppressive agents)
Inactivated vaccines can be administered but may have reduced efficacy
Administering influenza vaccine annually is usually recommended, even during chemotherapy, as influenza can be severe in this population.
After Chemotherapy:
Immune reconstitution after chemotherapy is a gradual process
Live attenuated vaccines can generally be resumed 3-12 months after the cessation of chemotherapy, depending on the intensity of treatment and specific agents used
A lymphocyte recovery to > 500/mm³ is often a prerequisite
Revaccination with inactivated vaccines is often recommended to ensure adequate antibody titers, typically starting 3-6 months post-therapy.
Specific Vaccine Considerations
Mmr And Varicella:
Live MMR and Varicella vaccines are usually deferred until at least 3-12 months post-chemotherapy or when immune function has sufficiently recovered (e.g., lymphocyte count > 500/mm³)
For children with a history of varicella or exposure, prompt post-exposure prophylaxis with VZIG (if indicated) is prioritized over immediate vaccination.
Influenza Vaccine:
Annual influenza vaccination is recommended for all immunocompromised children, including those on chemotherapy, ideally before flu season begins
Inactivated influenza vaccine is safe
If the child is vaccinated during chemotherapy, antibody response may be suboptimal, and revaccination post-therapy may be considered.
Bcg Vaccine:
BCG vaccine is a live attenuated vaccine and is generally contraindicated in children receiving immunosuppressive therapy due to the risk of disseminated BCG infection
It is typically administered at birth in endemic areas
interruption of schedule for immunocompromised children needs careful consideration.
Rotavirus Vaccine:
Live oral rotavirus vaccines are generally not recommended for children undergoing active chemotherapy due to theoretical risks of intussusception and vaccine-induced gastroenteritis in an immunocompromised state
Their use should be individualized based on risk-benefit assessment.
Special Populations
Hematopoietic Stem Cell Transplant Recipients:
Vaccination schedules are significantly altered for HSCT recipients
A complex, multi-phase re-vaccination protocol is initiated post-transplant, beginning approximately 6-12 months after engraftment, with a gradual reintroduction of inactivated and then live vaccines.
Solid Organ Transplant Recipients:
Similar to HSCT, immunosuppression necessitates a structured re-vaccination program post-transplant, carefully timed to avoid live vaccines during periods of intense immunosuppression.
Primary Immunodeficiency Disorders:
Vaccination guidelines for PID are highly specific to the type of defect
Live vaccines are often contraindicated in T-cell defects but may be permissible in certain B-cell disorders
Careful immunological assessment is paramount.
Key Points
Exam Focus:
The timing of live attenuated vs
inactivated vaccines around chemotherapy cycles and the definition of immune recovery are critical exam points
DNB/NEET SS questions often involve scenarios where the student must determine if a vaccine is safe or when it should be administered.
Clinical Pearls:
Always consult the latest guidelines from organizations like the Indian Academy of Pediatrics (IAP), CDC, or AAP
Maintain detailed immunization records and create a personalized vaccination plan for each immunocompromised child
Consider family members (cocooning) and healthcare providers for influenza and other relevant vaccinations.
Common Mistakes:
Administering live vaccines during periods of profound immunosuppression
Failing to revaccinate after completion of chemotherapy
Misinterpreting immune recovery criteria
Not considering the impact of specific chemotherapy agents on vaccine efficacy
Delaying necessary inactivated vaccines due to unwarranted concerns about safety.