Vaccine Responses in Adult Hematopoietic Stem Cell Transplant Recipients: A Comprehensive Review
Patients who recently received a stem cell transplantation are at greater risk for infection due to impairment of their immune system. In order to prevent severe infection, these patients are vaccinated after their stem cell transplantation with childhood immunization vaccines. Timing of this vaccination is important in order to be effective and obtain proper immune response. Postponement of vaccination would lead to better immune response but would also cause longer-lasting risk of infection. This review describes available data on the timing of vaccination and its vaccine responses. Optimal timing of vaccination might require an individualized approach per patient.
Hematopoietic stem cell transplantation (HSCT) is a promising and often the only curative option for patients with hematological malignancies . Post-HSCT, the immune system is temporarily suppressed due to prior conditioning and usage of immunosuppressive medication, resulting in infection-derived complications being a major cause of transplant-related mortality . Furthermore, pre-HSCT established immunity against vaccine-preventable diseases might be diminished through transplantation. To avoid infections, preventive strategies such as antibiotics, antiviral and antifungal prophylaxis and post-HSCT vaccination are recommended. Vaccination regimens for childhood immunization are clearly described in international guidelines, yet optimal timing of the vaccination is less clearly described and variable among guidelines [3,4,5,6,7].
Timing appears to play an important role in vaccine effectiveness. Vaccination before proper immune reconstitution may impair vaccine responses. However, as the risk of infection increases with time, postponing revaccination unnecessarily is undesirable [8,9]. Furthermore, recommendations for allogeneic HSCT (alloHSCT) and autologous HSCT (autoHSCT) recipients are uniform, whereas immunologic memory and immune reconstitution differ . In daily practice, post-autoHSCT recipients are either not vaccinated or receive vaccination conforming with the post-alloHSCT guidelines. Insight into vaccine responses to childhood immunization vaccines related to timing of the vaccination is needed. The aim of the present review was to evaluate the current literature on optimal timing of vaccination, vaccine schedule and vaccine types post-HSCT in relation to vaccine responses.
造血干细胞移植 (HSCT) 是血液系统恶性肿瘤患者的一种有前途且通常是唯一的治愈选择 [ 1 ]。HSCT 后，由于事先调理和使用免疫抑制药物，免疫系统暂时受到抑制，导致感染衍生的并发症是移植相关死亡率的主要原因 [ 2]。此外，HSCT 前建立的针对疫苗可预防疾病的免疫力可能会通过移植而减弱。为避免感染，建议采取预防策略，例如抗生素、抗病毒和抗真菌预防以及 HSCT 后接种疫苗。国际指南中清楚地描述了儿童免疫接种方案，但疫苗接种的最佳时机描述得不太清楚，并且在指南中有所不同 [ 3 , 4 , 5 , 6 , 7 ]。
时间似乎在疫苗有效性中起着重要作用。在适当的免疫重建之前接种疫苗可能会削弱疫苗反应。然而，随着感染的风险随着时间的推移而增加，不必要地推迟再次接种是不可取的 [ 8 , 9 ]。此外，对同种异体 HSCT (alloHSCT) 和自体 HSCT (autoHSCT) 受者的建议是一致的，而免疫记忆和免疫重建不同 [ 3]。在日常实践中，autoHSCT 后接受者要么未接种疫苗，要么接受符合 alloHSCT 后指南的疫苗接种。需要深入了解与疫苗接种时间相关的儿童免疫疫苗对疫苗的反应。本综述的目的是评估目前关于疫苗反应的最佳疫苗接种时间、疫苗时间表和 HSCT 后疫苗类型的文献。
In conclusion, vaccine responses to the childhood immunization vaccines in post-HSCT patients are lower as compared with healthy individuals, and therefore, measurement of response might be indicated. Furthermore, timing of vaccination is essential to reach optimal responses. Considering the influence of patient factors such as GVHD and usage of immunosuppressive drugs, an individualized approach might be necessary to optimize vaccine responses. However, guidance on how to initiate this individualized approach is currently lacking and further studies are needed.
Based on the included studies, general recommendations on timing of the childhood immunization vaccines post-alloHSCT are made and shown in Table 4. Due to overall lower response rates compared with healthy populations , assessment of response after vaccination is recommended. For autoHSCT recipients, no recommendations could be formed based on our review due to the scarcity of data.
总之，与健康个体相比，HSCT 后患者对儿童免疫疫苗的疫苗反应较低，因此可能需要对反应进行测量。此外，疫苗接种的时机对于达到最佳反应至关重要。考虑到 GVHD 和免疫抑制药物使用等患者因素的影响，可能需要采用个体化方法来优化疫苗反应。然而，目前缺乏关于如何启动这种个性化方法的指导，需要进一步研究。
根据纳入的研究，就 alloHSCT 后儿童免疫疫苗的时机提出了一般性建议，并显示在表 4中。由于与健康人群相比总体反应率较低 [ 47 ]，建议评估疫苗接种后的反应。对于 autoHSCT 接受者，由于数据稀缺，无法根据我们的审查形成建议。
关键词： 造血干细胞移植,疫苗接种,疫苗反应, hematopoietic stem cell transplantation,vaccination, vaccine response