Vaccine Immunity and Immune Reconstitution in Children After Hematopoietic Stem Cell Transplantation: A Retrospective Single-center Study

To the Editor: Infections by vaccine-preventable diseases constitute a threat for children after hematopoietic stem cell transplant (HSCT) due to a loss of specific immunity.1,2 Revaccination is an important strategy to improve survival in this population.3 Current guidelines of the European Conference on Infections in Leukaemia,4 the Infectious Diseases Society of America5 and, in Switzerland, the Federal Office of Public Health6 recommend vaccinations at fixed time-points beginning 3 to 6 months after HSCT. Our study, conducted at the Children's Hospital of Geneva after ethics approval (CCER 2020-01581) between January 2015 and December 2019, retrospectively assessed antigen-specific vaccine seroprotection and lymphocyte subpopulation recovery post-HSCT, aiming to optimize post-transplant vaccination schedules. We included children aged 0 to 18 years at the time of HSCT. On the basis of the Swiss recommendations,6 our center has developed a revaccination protocol postpediatric HSCT. This includes vaccinations against Streptococcus pneumoniae, diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b (Hib) (for children below 5 years), and hepatitis B at 3 months post-HSCT, followed by regular (at least at 6 and 12 months) vaccine serology for pneumococcus, tetanus, diphtheria, Hib for children below 5 years, and booster doses according to serology results. Vaccinations against measles and varicella are initiated at 24 months post-HSCT if there is no contraindication (such as graft versus host disease [GVHD]), in case of negative serology, and if CD4 cell levels >700/μL, followed by a booster dose 1 month later. Meningococcal, human papillomavirus and tick-borne encephalitis vaccines are administered 12 months post-HSCT. We analyzed 28 transplantations, with a median age of 5 years at transplant. The predominant stem cell source was bone marrow, with most patients receiving allogenic stem cells from HLA-matched unrelated donors. The majority underwent myeloablative conditioning, with a significant proportion experiencing acute (32%) and chronic GVHD (25%). The kinetics of the immune reconstitution showed varying trends depending on age (Fig. 1). All children achieved normal levels of B and T cells within 12 months after the transplantation. During the first year post-HSCT, vaccine-induced protection remained robust for tetanus and Hib. However, the level of protection against pneumococcus was insufficient, with rates ranging from 54% at 3 months to 70% at 12 months post-HSCT. Furthermore, the study revealed a decline in seroprotection against varicella and measles at 12 months post-HSCT, with rates dropping to 73% and 44%, respectively. These findings suggest that current vaccination guidelines may need revision to diminish the risk of invasive pneumococcal disease, as well as varicella and measles, in the year following HSCT.FIGURE 1: Concentrations of immune cells at baseline and 3, 6, 9, 12 months post-HSCT in pediatric patients, stratified by age groups according to age-based normal reference ranges7 (in green). (A) total lymphocytes, (B) total T cells, (C) CD4+ T cells, (D) CD8+ T cells, and (E) CD19 B cell. HSCT indicates hematopoietic stem cell transplant.Further studies should assess the safety and effectiveness of earlier administration of live-attenuated vaccines, possibly around 12 months post-HSCT, in the absence of contraindications such as GVHD. We recommend pre-HSCT vaccine-specific serology assessments, administering PCV13 pre-HSCT if necessary, followed by systematic post-HSCT doses and booster doses based on serology. The combined DTPa-IPV±Hib±HBV vaccine should be given at 6 and 8 months post-HSCT, with further vaccinations guided by 12-month serology results. Larger prospective studies are needed to explore individualized vaccination programs based on post-HSCT vaccine serology to enhance vaccine protection in this at-risk population.