How to structure an effective HSCT vaccine programme?
Notwithstanding the fact that several guidelines have been established for vaccination in patients who underwent a haematopoietic stem cell transplantation, several issues persist that hamper an effective implementation of a vaccination programme. During her presentation at the 46th Annual Meeting of the EBMT, Prof. Cordonnier shared her knowledge on how a vaccination programme should be organised, which vaccines should be selected, the importance of vaccination timing as well as monitoring of the response to vaccines in transplanted patients.
The aim of a vaccination program after HSCT is to reduce vaccine-preventable diseases and hospitalisation in order to save lives of HSCT recipients.1 In addition to this, vaccination also supports the development of herd immunity of the population.1 To date, the most commonly used vaccination guidelines in HSCT recipients consist of the IDSA Clinical Practice Guidelines for Vaccination of the Immunocompromised Host and the more recent guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7).2,3 Overall, vaccine selection and the timing of vaccination should be based on the available data on infections in HSCT (with respect to risk and timing of infections), information on efficacy and safety of the vaccines and specific vaccination guidelines. In addition to this, individual patient parameters should also be taken into consideration.1
An effective vaccination schedule
In general, all vaccines recommended in the general population should also be considered for HSCT patients. However, the timing of the vaccination in HSCT patients is much more critical. As recommended in the ECIL 7 guidelines, most transplanted HSCT patients have a very packed vaccination schedule during the first year after their transplantation. However, some patients may have good reasons to postpone vaccinations. Good arguments for such a postponement include a treatment with rituximab, the presence of profound hypogammaglobulinemia or other unstable conditions, an ongoing treatment with anti-thymocyte globulin the development of previous serious adverse events with a given vaccine. In contrast, however, postponing vaccination in patients with a perfectly controlled graft-versus-host disease (GvHD) is not recommended as most patients with GvHD still respond to T-cell dependent vaccines. Moreover, these patients are at the highest risk of infections and will most likely benefit the most from vaccination. To date, there are only rare indications to postpone or avoid vaccines and more data on vaccinations in different types of HSCT are pending. Therefore, the same vaccination schedule should be applied to all HSCT recipients.
Special care is warranted when using live-attenuated vaccines (LAVs) such as the measles-mumps-rubella (MMR) and varicella-zoster virus (VZV) vaccines or in exceptional cases where a vaccination against yellow fever is required. These LAVs can only be used in situations where a non-LAV alternative is not available. In general, LAVs are contra-indicated within the first 24 months after HCT. In addition, with the use of LAVs caution in warranted in seronegative recipients and patients should not suffer from GvHD, take immunosuppressive medicines and should not be in relapse. Finally, patients should not have received subcutaneous or intravenous immunoglobulins in the past 3-8 months.1
When considering vaccination in paediatric HSCT patients it is important to note that these patients usually respond better to vaccines than adults and that their responses are even close to those of healthy children. Exceptions to this rule consist of MMR and VZV LAVs. Importantly, however, young patients do have a higher risk for post-vaccine fever and local reactions. Although there are less data available in children than in adult HSCT recipients, Prof. Cordonnier recommends to use the same vaccination schedule for children and adults, with the exception of vaccinations for flu, HPV, Neisseria meningitidis and polio.1
Response to vaccination
The individual serology before vaccination should not be routinely assessed for regular vaccines planned during the first year of transplant, nor for the annual flu vaccination. In contrast, serological assessment can be useful when vaccinations for HBV (according to HBV serology, as of six months after transplantation) or LAVs are considered. After vaccination, no assessment of the individual antibody response is performed for vaccinations where the expected response is at least 90%. Nevertheless, assessment of individual responses may be very important to decide of additional doses/series and assess protection after HBV, MMR or VZV vaccination. In addition, it may be useful to look for pneumococcal antibodies after 24 months in patients with GvHD or other causes of poor immunity.1
Finally, HSCT donors should be vaccinated according to the recommended schedule in their country and it is contra-indicated to use LAVs within the four weeks preceding donation due to the risk of transmission of the pathogen to the graft.1
Conclusions
In order to provide a good vaccination programme, healthcare providers should be “vaccine-believers” and have written procedures for vaccination. Vaccinations should already be announced at the pre-transplant visit to educate patients and their families. Importantly, the programme should also include relatives of the patients and their healthcare personnel in order to create a circle of protection. Finally, vaccination should occur systematic and on time, while postponing vaccinations should only be the exception.1
References
1. Cordonnier C. How to structure an effective HSCT vaccine programme? Presented at EBMT 2020; Session E3-3.
2. Rubin LG, et al. Clinical Infectious Disease. 2014;58(3):e44-100.
3. Cordonnier C, et al. Lancet Infect Dis. 2019;19(6):e200-12.
