Review

Issue 3 - 2026

Indications for Vaccinations in Preschool Children Subjected to Thymectomy: An Exhaustive Immunological and Clinical Analysis

Authors

Keywords: DiGeorge Syndrome, Thymectomy, Vaccinations
Publication Date: 2026-09-30

Summary

Neonatal thymectomy during pediatric cardiothoracic surgery causes profound immunological consequences, primarily iatrogenic premature immunosenescence and impaired central tolerance.

This review analyzes the mechanisms of thymic deprivation, highlighting the loss of naive T-cells and the compensatory, oligoclonal expansion of memory T-cells. Given the heterogeneity of surgical cohorts, DiGeorge Syndrome (22q11.2DS) serves as a comparative clinical paradigm to establish evidence-based vaccination guidelines.

Inactivated vaccines are strongly recommended, although accelerated serological waning demands frequent monitoring and booster doses. Live attenuated vaccines (LAVs), including MMR and Varicella, can be safely administered if strict immunological thresholds (CD4+ ≥400 cells/mmc; CD8+ ≥200 cells/mmc) are surpassed. Conversely, live oral rotavirus and BCG vaccines are strictly contraindicated during severe lymphopenia or in the immediate post-operative window. Crucially, the live-attenuated Yellow Fever vaccine represents an absolute, lifelong contraindication due to the risk of fatal viscerotropic disease.

Rigorous flow cytometric and serological pre-vaccination evaluations, alongside permanent clinical documentation of thymic ablation, are essential to ensure safe immunization practices in this vulnerable pediatric cohort.

References

  1. Roosen J, Oosterlinck W, Meyns B. Routine thymectomy in congenital cardiac surgery changes adaptive immunity without clinical relevance. Interact Cardiovasc Thorac Surg 2015;20:101-106. https://doi.org/10.1093/icvts/ivu343.
  2. Cavalcanti NV, Palmeira P, Jatene MB, et al. Early Thymectomy Is Associated With Long-Term Impairment of the Immune System: A Systematic Review. Front Immunol 2021;12:774780. https://doi.org/10.3389/fimmu.2021.774780.
  3. Kooshesh KA, Foy BH, Sykes DB, et al. Health Consequences of Thymus Removal in Adults. N Engl J Med 2023;389:406-417. https://doi.org/10.1056/NEJMoa2302892.
  4. van den Broek T, Madi A, Delemarre EM, et al. Human neonatal thymectomy induces altered B-cell responses and autoreactivity. Eur J Immunol 2017;47:1970-1981. https://doi.org/10.1002/eji.201746971.
  5. Halnon NJ, Jamieson B, Plunkett M, et al. Thymic Function and Impaired Maintenance of Peripheral T Cell Populations in Children with Congenital Heart Disease and Surgical Thymectomy. Pediatr Res 2005;57:42-48. https://doi.org/10.1203/01.PDR.0000147735.19342.DE.
  6. Kymioni VM, Panagiotou P, Tzanoudaki M, et al. Long-Term Immune Alterations After Thymectomy in Early Childhood: A Case Series. Cureus 2025;17:e95517. https://doi.org/10.7759/cureus.95517.
  7. Prelog M, Keller M, Geiger R, et al. Thymectomy in early childhood: Significant alterations of the CD4+CD45RA+CD62L+ T cell compartment in later life. Clin Immunol 2009;130:123-132. https://doi.org/10.1016/j.clim.2008.08.023.
  8. Mancebo E, Clemente J, Sanchez J, et al. Longitudinal analysis of immune function in the first 3 years of life in thymectomized neonates during cardiac surgery. Clin Exp Immunol 2008;154:375-383. https://doi.org/10.1111/j.1365-2249.2008.03771.x.
  9. Eysteinsdottir JH, Freysdottir J, Haraldsson A, et al. The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life. Clin Exp Immunol 2004;136:349-355. https://doi.org/10.1111/j.1365-2249.2004.02437.x.
  10. Sauce D, Larsen M, Fastenackels S, et al. Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest 2009;119:3070-3078. https://doi.org/10.1172/JCI39269.
  11. Cramer A, Yang T, Riemann L, et al. Early-life thymectomy leads to an increase of granzyme-producing γδ T cells in children with congenital heart disease. Nat Commun 2024;15:9841. https://doi.org/10.1038/s41467-024-51673-3.
  12. Wickemeyer JL, Sekhsaria S. Prolonged severe immunodeficiency following thymectomy and radiation: a case report. J Med Case Rep 2014;8:457. https://doi.org/10.1186/1752-1947-8-457.
  13. van Oers NSC, Sullivan KE. The systemic effects of 22q11.2 deletion syndrome on immunity. J Hum Immun 2026;2:e20250190. https://doi.org/10.70962/jhi.20250190.
  14. Mustillo PJ, Sullivan KE, Chinn IK, et al. Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development. J Clin Immunol 2023;43:247-270. https://doi.org/10.1007/s10875-022-01418-y.
  15. Farpour L, Gualtieri R, Kotalova T, et al. Vaccine immunity in patients with 22q11.2 microdeletion syndrome. Pediatr Allergy Immunol 2025;36:e70043. https://doi.org/10.1111/pai.70043.
  16. Perez EE, Bokszczanin A, McDonald-McGinn D, et al. Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Pediatrics 2003;112:e325. https://doi.org/10.1542/peds.112.4.e325.
  17. Moylett EH, Wasan AN, Noroski LM, et al. Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. Clin Immunol 2004;112:106-112. https://doi.org/10.1016/j.clim.2004.02.008.
  18. Al-Sukaiti N, Reid B, Lavi S, et al. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J Allergy Clin Immunol 2010;126:868-869. https://doi.org/10.1016/j.jaci.2010.07.018.
  19. Lim SM, Shin JH, Baek JY, et al. Safety of Live Immunization in DiGeorge Syndrome: A Retrospective Single-Center Study in Korea, 2005–2021. Vaccines (Basel) 2022;10:2165. https://doi.org/10.3390/vaccines10122165.
  20. Hofstetter AM, Jakob K, Klein NP, et al. Live Vaccine Use and Safety in DiGeorge Syndrome. Pediatrics 2014;133:e946-e954. https://doi.org/10.1542/peds.2013-0831.
  21. Waters V, Peterson KS, LaRussa P. Live viral vaccines in a DiGeorge syndrome patient. Arch Dis Child 2007;92:519-520. https://doi.org/10.1136/adc.2006.097493.
  22. McGregor S, Boroditsky M, Blanchard-Rohner G, et al. Evaluation of rotavirus vaccine administration among a 22q11.2DS patient population. Allergy Asthma Clin Immunol 2022;18:50. https://doi.org/10.1186/s13223-022-00693-z.
  23. WHO. Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013-Recommendations. Vaccine 2015;33:76-77. https://doi.org/10.1016/j.vaccine.2014.05.040.
  24. McDonnell E, Habibi H. Yellow fever vaccination and the thymus in adults with congenital heart disease. International Int J Cardiol Congenit Heart Dis 2024;15:100494. https://doi.org/10.1016/j.ijcchd.2024.100494.
  25. Lindsey NP, Rabe IB, Miller ER, et al. Adverse event reports following yellow fever vaccination, 2007-13. J Travel Med 2016;23:taw045. https://doi.org/10.1093/jtm/taw045.
  26. Gershman MD, Staples JE, Bentsi-Enchill AD, et al. Viscerotropic disease: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2012;30:5038-5058. https://doi.org/10.1016/j.vaccine.2012.04.067.
  27. Ratti C, Greca AD, Bertoncelli D, et al. Prophylaxis protects infants with congenital heart disease from severe forms of RSV infection: an Italian observational retrospective study. Ital J Pediatr 2023;49:4. https://doi.org/10.1186/s13052-022-01399-z.
  28. Simões EAF, Madhi SA, Muller WJ, et al. Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials. Lancet Child Adolesc Health 2023;7:180-189. https://doi.org/10.1016/S2352-4642(22)00321-2.
  29. Lee B, Trusinska D, Ferdous S, et al. Real-world effectiveness and safety of nirsevimab, RSV maternal vaccine and RSV vaccines for older adults: a living systematic review and meta-analysis. Thorax 2025;80:838-848. https://doi.org/10.1136/thorax-2025-223376.
  30. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med 2022;386:837-846. https://doi.org/10.1056/NEJMoa2110275.
  31. Kreins AY, Dhalla F, Flinn AM, et al. European Society for Immunodeficiencies guidelines for the management of patients with congenital athymia. J Allergy Clin Immunol 2024;154:1391-1408. https://doi.org/10.1016/j.jaci.2024.07.031.
  32. Kurobe H, Tominaga T, Sugano M, et al. Complete but not partial thymectomy in early infancy reduces T-cell-mediated immune response: Three-year tracing study after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2013;145:656-662.e2. https://doi.org/10.1016/j.jtcvs.2012.12.015.
  33. Kesäläinen A, Rantanen R, Honkila M, et al. Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study. BMJ Paediatr Open 2024;8:e002651. https://doi.org/10.1136/bmjpo-2024-002651.

Downloads

Authors

Mattia Moratti - Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy https://orcid.org/0000-0003-1133-9563

Francesca Conti - Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy

How to Cite
Moratti, M., & Conti, F. (2026). Indications for Vaccinations in Preschool Children Subjected to Thymectomy: An Exhaustive Immunological and Clinical Analysis. Italian Journal of Pediatric Allergy and Immunology, 40(3). https://doi.org/10.53151/2531-3916/2026-2678
  • Abstract viewed - 0 times
  • pdf downloaded - 0 times