Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review
Abstract
1. Introduction
2. Methods
3. Hematopoietic Stem Cell Transplantation in Pediatric Recipients
3.1. Immune Reconstitution
3.2. Vaccine Adherence and Follow-Up in Transplant Patients
4. Chimeric Antigen Receptor T-Cell (CAR-T) Therapy and Infectious Risk: Implications for Immune Monitoring and Vaccination
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wohlschlaeger, A.; Levy, E.; Khan, R.N.; Heimall, J.; Fisher, B.T.; Metjian, T.A.; Elgarten, C.W.; Freedman, J.L. A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients. J. Pediatr. Hematol. Oncol. Nurs. 2023, 40, 259–264. [Google Scholar] [CrossRef] [PubMed]
- Miller, P.D.E.; de Silva, T.I.; Skinner, R.; Gilleece, M.; Peniket, A.; Hamblin, A.; Greenfield, D.; Anthias, C.; Peggs, K.; Madrigal, A.; et al. Routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: A survey of UK NHS programmes. Bone Marrow Transplant. 2017, 52, 775–777, Erratum in Bone Marrow Transplant. 2017, 52, 1082. [Google Scholar] [CrossRef] [PubMed]
- Kumar, D.; Humar, A.; Plevneshi, A.; Siegal, D.; Franke, N.; Green, K.; McGeer, A.; Toronto Invasive Bacterial Diseases Network. Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: A decade of prospective population-based surveillance. Bone Marrow Transplant. 2008, 41, 743–747. [Google Scholar] [CrossRef] [PubMed]
- Ge, Y.L.; Zhai, X.W.; Zhu, Y.F.; Wang, X.S.; Xia, A.M.; Li, Y.F.; Zeng, M. Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015. Chin. Med. J. 2017, 130, 1320–1326. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Miller, P.; Patel, S.R.; Skinner, R.; Dignan, F.; Richter, A.; Jeffery, K.; Khan, A.; Heath, P.T.; Clark, A.; Orchard, K.; et al. Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children’s cancer and Leukaemia Group (CCLG), and British Infection Association (BIA). J. Infect. 2023, 86, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Danino, D.; Stanek, J.R.; Rangarajan, H.; Ardura, M.I. Hospitalizations for vaccine-preventable infections among pediatric hematopoietic cell transplantation recipients in the first 5 years after transplantation. Bone Marrow Transplant. 2021, 56, 2656–2663. [Google Scholar] [CrossRef] [PubMed]
- Neemann, K.A.; Sato, A.I. Vaccinations in children with hematologic malignancies and those receiving hematopoietic stem cell transplants or cellular therapies. Transpl. Infect. Dis. 2023, 25 (Suppl. 1), e14100. [Google Scholar] [CrossRef] [PubMed]
- Kansagra, A.J.; Frey, N.V.; Bar, M.; Laetsch, T.W.; Carpenter, P.A.; Savani, B.N.; Heslop, H.E.; Bollard, C.M.; Komanduri, K.V.; Gastineau, D.A.; et al. Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation. Biol. Blood Marrow Transplant. 2019, 25, e76–e85. [Google Scholar] [CrossRef]
- Van Veen, K.E.; Brouwer, M.C.; van der Ende, A.; van de Beek, D. Bacterial meningitis in hematopoietic stem cell transplant recipients: A population-based prospective study. Bone Marrow Transplant. 2016, 51, 1490–1495. [Google Scholar] [CrossRef] [PubMed]
- Shigayeva, A.; Rudnick, W.; Green, K.; Chen, D.K.; Demczuk, W.; Gold, W.L.; Johnstone, J.; Kitai, I.; Krajden, S.; Lovinsky, R.; et al. Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs. Clin. Infect. Dis. 2016, 62, 139–147. [Google Scholar] [CrossRef] [PubMed]
- Cordonnier, C.; Bernaudin, J.F.; Bierling, P.; Huet, Y.; Vernant, J.P. Pulmonary complications occurring after allogeneic bone marrow transplantation. A study of 130 consecutive transplanted patients. Cancer 1986, 58, 1047–1054. [Google Scholar] [CrossRef]
- Ljungman, P.; de la Camara, R.; Perez-Bercoff, L.; Abecasis, M.; Nieto Campuzano, J.B.; Cannata-Ortiz, M.J.; Cordonnier, C.; Einsele, H.; Gonzalez-Vicent, M.; Espigado, I.; et al. Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients. Haematologica 2011, 96, 1231–1235. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Beck, C.R.; McKenzie, B.C.; Hashim, A.B.; Harris, R.C.; University of Nottingham Influenza and the ImmunoCompromised (UNIIC) Study Group; Nguyen-Van-Tam, J.S. Influenza vaccination for immunocompromised patients: Systematic review and meta-analysis by aetiology. J. Infect. Dis. 2012, 206, 1250–1259. [Google Scholar] [CrossRef] [PubMed]
- Mallet, V.; van Bömmel, F.; Doerig, C.; Pischke, S.; Hermine, O.; Locasciulli, A.; Cordonnier, C.; Berg, T.; Moradpour, D.; Wedemeyer, H.; et al. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: Recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). Lancet Infect. Dis. 2016, 16, 606–617. [Google Scholar] [CrossRef] [PubMed]
- Shanis, D.; Anandi, P.; Grant, C.; Bachi, A.; Vyas, N.; Merideth, M.A.; Pophali, P.A.; Koklanaris, E.; Ito, S.; Savani, B.N.; et al. Risks factors and timing of genital human papillomavirus (HPV) infection in female stem cell transplant survivors: A longitudinal study. Bone Marrow Transplant. 2018, 53, 78–83. [Google Scholar] [CrossRef] [PubMed]
- Haynes, A.S.; Curtis, D.J.; Campbell, K.; Giller, R.H.; Quinones, R.R.; Verneris, M.R.; Abzug, M.J. An Immune Recovery-Based Revaccination Protocol for Pediatric Hematopoietic Stem Cell Transplant Recipients: Revaccination Outcomes Following Pediatric HSCT. Transplant. Cell Ther. 2021, 27, 317–326. [Google Scholar] [CrossRef]
- Greco, R.; Ciceri, F.; Noviello, M.; Bondanza, A.; Vago, L.; Oliveira, G.; Peccatori, J.; Cieri, N.; Ruggeri, A.; Koehl, U.; et al. Immune monitoring in allogeneic hematopoietic stem cell transplant recipients: A survey from the EBMT-CTIWP. Bone Marrow Transplant. 2018, 53, 1201–1205. [Google Scholar] [CrossRef] [PubMed]
- Wiegering, V.; Eyrich, M.; Winkler, B.; Schlegel, P.G. Comparison of Immune Reconstitution After Allogeneic Versus Autologous Stem Cell Transplantation in 182 Pediatric Recipients. J. Pediatr. Hematol. Oncol. 2019, 41, e302–e307. [Google Scholar] [CrossRef]
- Cecinati, V.; Principi, N.; Brescia, L.; Esposito, S. Antibiotic prophylaxis in children with cancer or who have undergone hematopoietic cell transplantation. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Olkinuora, H.; von Willebrand, E.; Kantele, J.M.; Vainio, O.; Talvensaari, K.; Saarinen-Pihkala, U.; Siitonen, S.; Vettenranta, K. The impact of early viral infections and graft-versus-host disease on immune reconstitution following paediatric stem cell transplantation. Scand. J. Immunol. 2011, 73, 586–593. [Google Scholar] [CrossRef] [PubMed]
- Forlenza, C.J.; Small, T.N. Live (Vaccines) from New York. Bone Marrow Transplant. 2013, 48, 749–754. [Google Scholar] [CrossRef] [PubMed]
- Small, T.N.; Zelenetz, A.D.; Noy, A.; Rice, R.D.; Trippett, T.M.; Abrey, J.D.; Portlock, C.S.; McCullagh, E.J.; Vanak, J.M.; Mulligan, A.M.; et al. Pertussis immunity and response to tetanus-reduced diphtheria-reduced pertussis vaccine (Tdap) after autologous peripheral blood stem cell transplantation. Biol. Blood Marrow Transplant. 2009, 15, 1538–1542. [Google Scholar] [CrossRef]
- Ljungman, P.; Cordonnier, C.; Einsele, H.; Englund, J.; Machado, C.M.; Storek, J.; Small, T. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009, 44, 521–526. [Google Scholar] [CrossRef]
- Amarin, J.Z.; Dulek, D.E.; Simmons, J.; Hayek, H.; Chappell, J.D.; Nochowicz, C.H.; Kitko, C.L.; Schuster, J.E.; Muñoz, F.M.; Bocchini, C.E.; et al. Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients. Blood Adv. 2024, 8, 1880–1892. [Google Scholar] [CrossRef]
- Al-Antary, E.; Henry, M.; Spruit, J.; Yankelevich, M.; Chu, R.; Ravindranath, Y.; Savaşan, S. Patterns and correlates of preserved humoral immunity to vaccines in children following allogeneic hematopoietic stem cell transplantation. Pediatr. Transplant. 2021, 25, e13936. [Google Scholar] [CrossRef] [PubMed]
- Ozboru Askan, O.; Ozden, T.A.; Karasu Tezcan, G.; Keskindemirci, G.; Bakir, A.; Tugcu, D.; Pekun, F.; Yesilipek, A.; Gokcay, E.G. Vaccine Adherence and Postvaccination Serological Status of Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience. J. Pediatr. Hematol. Oncol. 2023, 45, e370–e377. [Google Scholar] [CrossRef] [PubMed]
- Sattler, C.; Hoffmann, P.; Herzberg, P.Y.; Weber, D.; Holler, B.; Fehn, U.; Plentz, A.; Beckhove, P.; Winkler, J.; Edinger, M.; et al. Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation—A single center retrospective efficacy analysis. Vaccine 2021, 39, 4742–4750. [Google Scholar] [CrossRef]
- Lee, E.S.; Kim, S.K.; Han, S.B.; Lee, J.W.; Chung, N.G.; Cho, B.; Jeong, D.C.; Kang, J.H. Serologic status and vaccine response against hepatitis B virus after allogeneic hematopoietic cell transplantation in pediatric patients. Asian Pac. J. Allergy Immunol. 2023, 41, 80–88. [Google Scholar] [CrossRef]
- Olkinuora, H.; Käyhty, H.; Davidkin, I.; Roivainen, M.; Ölander, R.-M.; Kantele, J.M.; Siitonen, S.; Vettenranta, K. Immunity after (re)vaccination of paediatric patients following haematopoietic stem cell transplantation. Acta Paediatr. 2012, 101, e373–e377. [Google Scholar] [CrossRef] [PubMed]
- Kondolot, M.; Yilmaz, E.; Erdog Sahin, N.; Ozcan, A.; Kaynar, L.; Unal, E.; Karakukcu, M. Antibody Response against Vaccine Antigens in Children after TCRαβ-Depleted Haploidentical Stem Cell Transplantation: Is It Similar to That in Recipients with Fully Matched Donors? Transplant. Cell Ther. 2023, 29, 128.e1–128.e9. [Google Scholar] [CrossRef] [PubMed]
- Pettke, A.; Jocham, S.; Wiener, A.; Löcken, A.; Groenefeld, J.; Ahlmann, M.; Groll, A.H. Vaccination against influenza at a European pediatric cancer center: Immunization rates and attitudes among staff, patients, and their families. Support. Care Cancer 2017, 25, 3815–3822. [Google Scholar] [CrossRef] [PubMed]
- Freedman, J.L.; Reilly, A.F.; Powell, S.C.; Bailey, L.C. Quality improvement initiative to increase influenza vaccination in pediatric cancer patients. Pediatrics 2015, 135, e540–e546. [Google Scholar] [CrossRef] [PubMed]
- Cordonnier, C.; Einarsdottir, S.; Cesaro, S.; Di Blasi, R.; Mikulska, M.; Rieger, C.; de Lavallade, H.; Gallo, G.; Lehrnbecher, T.; Engelhard, D.; et al. Vaccination of haemopoietic stem cell transplant recipients: Guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect. Dis. 2019, 19, e200–e212. [Google Scholar] [CrossRef] [PubMed]
- Seale, H.; Leask, J.; MacIntyre, C.R. Attitudes amongst Australian hospital healthcare workers towards seasonal influenza and vaccination. Influenza Other Respir. Viruses 2010, 4, 41–46. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Astray-Mochales, J.; López de Andres, A.; Hernandez-Barrera, V.; Rodríguez-Rieiro, C.; Carrasco Garrido, P.; Esteban-Vasallo, M.D.; Domínguez-Berjón, M.F.; Jimenez-Trujillo, I.; Jiménez-García, R. Influenza vaccination coverages among high risk subjects and health care workers in Spain. Results of two consecutive National Health Surveys (2011–2014). Vaccine 2016, 34, 4898–4904. [Google Scholar] [CrossRef] [PubMed]
- Esposito, S.; Tremolati, E.; Bellasio, M.; Chiarelli, G.; Marchisio, P.; Tiso, B.; Mosca, F.; Pardi, G.; Principi, N. Attitudes and knowledge regarding influenza vaccination among hospital health workers car- ing for women and children. Vaccine 2007, 25, 5283–5289. [Google Scholar] [CrossRef] [PubMed]
- Silva, P.M.D.; Silva, É.M.D.; Simioni, A.J.; Souza, M.P.; Colturato, V.A.R.; Machado, C.M. Difficulties in the revaccination program of hematopoietic stem cell transplantation recipients. Rev. Inst. Med. Trop. Sao Paulo 2017, 59, e69. [Google Scholar] [CrossRef]
- Nelson, J.C.; Bittner, R.C.; Bounds, L.; Zhao, S.; Baggs, J.; Donahue, J.G.; Hambidge, S.J.; Jacobsen, S.J.; Klein, N.P.; Naleway, A.L.; et al. Compliance with multiple-dose vaccine schedules among older children, adolescents, and adults: Results from a vaccine safety datalink study. Am. J. Public Health 2009, 99 (Suppl. 2), S389–S397. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Buchbinder, D.; Brazauskas, R.; Bo-Subait, K.; Ballen, K.; Parsons, S.; John, T.; Hahn, T.; Sharma, A.; Steinberg, A.; D’SOuza, A.; et al. Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research. Biol. Blood Marrow Transplant. 2020, 26, 553–561. [Google Scholar] [CrossRef]
- Hudspeth, M.P.; Hill, T.N.; Lewis, J.A.; Van Meter, E.; Ragucci, D. Post-hematopoietic stem cell transplant immunization practices in the Pediatric Blood and Marrow Transplant Consortium. Pediatr. Blood Cancer 2010, 54, 970–975. [Google Scholar] [CrossRef] [PubMed]
- Ariza-Heredia, E.J.; Gulbis, A.M.; Stolar, K.R.; Kebriaei, P.; Shah, D.P.; McConn, K.K.; Champlin, R.E.; Chemaly, R.F. Vaccination guidelines after hematopoietic stem cell transplantation: Practitioners’ knowledge, attitudes, and gap between guidelines and clinical practice. Transpl. Infect. Dis. 2014, 16, 878–886. [Google Scholar] [CrossRef] [PubMed]
- Yakoub-Agha, I.; Chabannon, C.; Bader, P.; Basak, G.W.; Bonig, H.; Ciceri, F.; Corbacioglu, S.; Duarte, R.F.; Einsele, H.; Hudecek, M.; et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: Best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica 2020, 105, 297–316. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Cao, Z.; Chen, Z.; Wang, Y.; He, H.; Xiao, P.; Hu, S.; Lu, J.; Li, B. Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia. Clin. Exp. Med. 2024, 24, 87. [Google Scholar] [CrossRef]
- Los-Arcos, I.; Iacoboni, G.; Aguilar-Guisado, M.; Alsina-Manrique, L.; de Heredia, C.D.; Fortuny-Guasch, C.; García-Cadenas, I.; García-Vidal, C.; González-Vicent, M.; Hernani, R.; et al. Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: A position paper. Infection 2021, 49, 215–231. [Google Scholar] [CrossRef] [PubMed]
- Shahid, Z.; Jain, T.; Dioverti, V.; Pennisi, M.; Mikkilineni, L.; Thiruvengadam, S.K.; Shah, N.N.; Dadwal, S.; Papanicolaou, G.; Hamadani, M.; et al. Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies. Transplant. Cell Ther. 2024, 30, 955–969. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Li, H.; Song, X.; Qi, K.; Cheng, H.; Cao, J.; Shi, M.; Yan, Z.; Jing, G.; Pan, B.; et al. Kinetics of immune reconstitution after anti-CD19 chimeric antigen receptor T cell therapy in relapsed or refractory acute lymphoblastic leukemia patients. Int. J. Lab. Hematol. 2021, 43, 250–258. [Google Scholar] [CrossRef] [PubMed]
- Deyà-Martínez, A.; Alonso-Saladrigues, A.; García, A.P.; Faura, A.; Torrebadell, M.; Vlagea, A.; Català, A.; Esteve-Solé, A.; Juan, M.; Rives, S.; et al. Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia. Bone Marrow Transplant. 2021, 56, 376–386. [Google Scholar] [CrossRef]
- Walti, C.S.; Krantz, E.M.; Maalouf, J.; Boonyaratanakornkit, J.; Keane-Candib, J.; Joncas-Schronce, L.; Stevens-Ayers, T.; Dasgupta, S.; Taylor, J.J.; Hirayama, A.V.; et al. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies. JCI Insight 2021, 6, e146743. [Google Scholar] [CrossRef]
- Gonzalez, M.A.; Boonyaratanakornkit, J.; Bhatti, A.; Keane-Candib, J.; Huang, M.-L.; Campbell, V.; Goecker, E.; Ibrahimi, S.; Hecht, J.; McClurkan, C.; et al. Comparison of humoral and T-cell response after SarsCov-2 vaccination among patients before and after chimeric antigen receptor-modified T cell (CAR-T cell) therapy. Transplant. Cell Ther. 2022, 28, S212–S213. [Google Scholar] [CrossRef]
- Walti, C.S.; Loes, A.N.; Shuey, K.; Krantz, E.M.; Boonyaratanakornkit, J.; Keane-Candib, J.; Loeffelholz, T.; Wolf, C.R.; Taylor, J.J.; Gardner, R.A.; et al. Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: A prospective observational study. J. Immunother. Cancer 2021, 9, e003428. [Google Scholar] [CrossRef]
- Khawaja, F.; Papanicolaou, G.; Dadwal, S.; Pergam, S.A.; Wingard, J.R.; El Boghdadly, Z.; Abidi, M.Z.; Waghmare, A.; Shahid, Z.; Michaels, L.; et al. Frequently asked questions on Coronavirus Disease 2019 vaccination for hematopoietic cell transplantation and chimeric antigen receptor T-cell recipients from the american society for transplantation and cellular therapy and the American Society of Hematology. Transplant. Cell Ther. 2023, 29, 10–18. [Google Scholar] [CrossRef]
- Riccò, M.; Abu-Raya, B.; Icardi, G.; Spoulou, V.; Greenberg, D.; Pecurariu, O.F.; Hung, I.F.; Osterhaus, A.; Sambri, V.; Esposito, S. Respiratory Syncytial Virus: A WAidid Consensus Document on New Preventive Options. Vaccines 2024, 12, 1317. [Google Scholar] [CrossRef] [PubMed]
- Principi, N.; Perrone, S.; Esposito, S. Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review. Vaccines 2025, 13, 717. [Google Scholar] [CrossRef] [PubMed]
- Esposito, S.; Abu Raya, B.; Baraldi, E.; Flanagan, K.; Martinon Torres, F.; Tsolia, M.; Zielen, S. RSV Prevention in All Infants: Which Is the Most Preferable Strategy? Front. Immunol. 2022, 13, 880368. [Google Scholar] [CrossRef] [PubMed]
- Esposito, S.; Abu-Raya, B.; Bonanni, P.; Cahn-Sellem, F.; Flanagan, K.L.; Martinon Torres, F.; Mejias, A.; Nadel, S.; Safadi, M.A.P.; Simon, A. Coadministration of Anti-Viral Monoclonal Antibodies with Routine Pediatric Vaccines and Implications for Nirsevimab Use: A White Paper. Front. Immunol. 2021, 12, 708939. [Google Scholar] [CrossRef]
Type of Vaccine | Clinical Impact of the Disease | Recommendation | Features of Pediatric Population | Vaccine Efficacy |
---|---|---|---|---|
PCV | The risk of invasive pneumococcal disease (meningitis and pneumonia) is around 3.8–5.0 of 1000 transplant cases after autologous HCT and 8.2–9.0 of 1000 transplant cases after allogeneic HCT. | From 3 months after transplantation, three doses of PCV at 1-month intervals are recommended, followed by a dose of PPSV23 6 months later. | The administration of PPSV23 is recommended after the administration of three doses of PCV to broaden the spectrum of vaccination. | The response to three doses of PCV is 64–98%. |
Hib | Hib can cause pneumonia, sinusitis, and bacteremia soon after transplantation. | From 3 months after transplantation, three doses of Hib vaccine at 1-month intervals are recommended. No preference on the type of vaccine (conjugated with tetanus-protein or diphtheria-protein). Alternatively, to decrease the overall number of vaccine doses, three doses of a combined diphtheria–tetanus–pertussis–Hib vaccine from 6 months after the transplantation. | NA | The response to Hib conjugate vaccines is 80–95%. |
Neisseria meningitidis | The risk of invasive disease (meningitis) is higher after HCT. No clear data available in the literature. | From 6 months after transplantation, at least two doses of either a monovalent or tetravalent C vaccine and meningococcal B vaccine in accordance with country recommendations. | Children and adolescents are the main at-risk population. | The response to three doses of MCV-4 administered 12 months. After autologous HCT or 18 months after allogeneic transplantation is 100%. No data about MenB vaccine response. |
Diphtheria and tetanus | Tetanus: The exposure to tetanus in the environment is a real risk for HCT patients. Diphtheria: There are very limited published data on Diphteritis in HCT. Ongoing vaccination is critical for immunity. Pertussis: There are very limited published data on pertussis in HCT. | From 6 months after transplantation, three doses of diphtheria–tetanus vaccine at 1–2-month intervals are recommended. Booster doses should be administered according to country recommendations. The ECIL group recommends considering the addition of pertussis toxoid to each dose of the diphtheria–tetanus vaccine. | DT vaccines should be preferred over Td vaccines. | The response to tetanus vaccine administered at 6–12 months after the transplantation is 85–100% after three doses. The response rate to diphtheria vaccine is 70–100% after three doses administered from 3 months after allogeneic HCT and 18 months to 10 years after autologous HCT No data about anti-pertussis vaccine response. |
IIV |
| In the first year after HCT, two doses of IIV given one month apart are recommended to enhance immunogenicity, followed by a single annual dose at the start of each influenza season for as long as the patient remains immunocompromised. | Additional measures are also fundamental (e.g., respiratory isolation, rapid diagnostic tests in case of symptoms, and post-exposure antivirals). The intranasal influenza live-attenuated vaccine is contraindicated after HCT. | A systematic review and meta-analysis showed significantly lower odds of influenza-like illness after vaccination in transplant recipients compared with patients receiving placebo or no vaccination. Seroconversion and seroprotection are lower in transplant recipients compared with immunocompetent controls |
HBV | Viral hepatitis can be life-threatening in patients with HCT recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. | Although most recent guidelines do not consider serostatus a decisive factor for revaccination, patients who are HBV-seronegative prior to transplantation, as well as those who were vaccinated before transplant but lose immunity within 6 months afterward, should be revaccinated according to national recommendations, typically with a three-dose series initiated 6–12 months post-transplant and administered at 0, 1, and 6 months, with post-vaccination serology used to confirm response. | Before transplant, patients who are negative for all HBV markers and are transplanted with a graft from an anti-HBc-positive donor should be vaccinated if possible and could additionally receive anti-HBV immunoglobulins. Patients infected with HBV before HCT (HBsAg-negative and anti-HBc-positive) should be assessed regularly for anti-HBs antibody titers and should be vaccinated if they have unprotective titers. If anti-HBs titers are <10 mIU/mL 1–2 months after the initial series of three vaccine doses, an additional series of three doses should be considered. Children should receive a standard pediatric dose (10 µg) of vaccine, and adolescents should receive 20 µg of the vaccine according to the summary of product characteristics of each vaccine. | The seroconversion rate was nearly 64%. |
HPV | Genital HPV disease is a significant late complication of alloHCT, occurring in one-third of women. In long-term survivors, second neoplasias are a significant complication after alloHCT. Cervix cancer is one of the most frequent. Squamous cell cancers, the commonest post-transplant solid tumors, are associated with HPV infection. | From 6 to 12 months after transplantation, recommendations for the general population in each country should be followed. | NA | The seroconversion rate was nearly 100%. |
IPV | NA Maintaining high vaccination coverage in all population groups remains an essential tool for keeping Europe polio-free. | From 6 to 12 months after transplantation, three doses of PV are recommended to be administered at 1–2-month intervals; booster doses should be administered according to country recommendations. | NA | The response to three doses of the vaccine administered 6 months after the transplant is 80–100% and long-lasting. |
Measles–mumps–rubella | Measles: Severe and also fatal measles infections (pneumonia, encephalitis) have been reported in HCT recipients.
Rubella: The main indication for rubella vaccination is prevention of congenital rubella in fertile women. Mumps: There are no reports of severe mumps occurring in HCT recipients. | Starting from 24 months post-transplant, live vaccines should be considered only in seronegative patients who are free of GVHD, off immunosuppressive therapy, without disease relapse, and with no recent administration of immunoglobulins. | Seronegative patients for measles should receive one dose of MMR; HCT recipients who are women, seronegative for rubella, and of childbearing potential should receive one dose of MMR; in case of a measles outbreak, MMR vaccination could be considered 12 months after transplantation in patients with low-grade immunosuppression | The response rate is 65–100% for measles, 50–87% for mumps, and 75–100% for rubella. |
VZV | VZV infections could be life-threatening after HCT. The risks are primary varicella infection (chickenpox) in seronegative patients and shingles and postherpetic neuralgia in seropositive patients. | From 24 months after transplantations, only in seronegative patients with no GvHD, no immunosuppressants, no relapse, and no recent administration of immunoglobulins. | Some patients developed vaccine-related varicella. | The response rate is around 65%, without a clear benefit of a second dose. |
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Zama, D.; Pedretti, L.; Capoferri, G.; Forestiero, R.; Lanari, M.; Esposito, S. Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review. Vaccines 2025, 13, 932. https://doi.org/10.3390/vaccines13090932
Zama D, Pedretti L, Capoferri G, Forestiero R, Lanari M, Esposito S. Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review. Vaccines. 2025; 13(9):932. https://doi.org/10.3390/vaccines13090932
Chicago/Turabian StyleZama, Daniele, Laura Pedretti, Gaia Capoferri, Roberta Forestiero, Marcello Lanari, and Susanna Esposito. 2025. "Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review" Vaccines 13, no. 9: 932. https://doi.org/10.3390/vaccines13090932
APA StyleZama, D., Pedretti, L., Capoferri, G., Forestiero, R., Lanari, M., & Esposito, S. (2025). Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review. Vaccines, 13(9), 932. https://doi.org/10.3390/vaccines13090932