Randomized Study of Early versus Late Immunization with Pneumococcal Conjugate Vaccine after Allogeneic Stem Cell Transplantation
Randomized Study of Early versus Late Immunization with Pneumococcal Conjugate Vaccine after Allogeneic Stem Cell Transplantation
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DOI：
10.1086/598324
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发表时间：
2009-05-15
影响因子：
11.8
通讯作者：
Ljungman, Per
中科院分区：
文献类型：
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作者：
Cordonnier, Catherine;Labopin, Myriam;Ljungman, Per
背景侵袭性肺炎球菌病是异基因干细胞移植后危及生命的并发症，至少20%的病例发生在移植后1年内。23价肺炎球菌多糖疫苗（PPV 23）的疗效有限，尤其是在移植后的第一年。预计结合疫苗的免疫反应比多糖疫苗更好，但疫苗接种的最佳时机尚未确定。我们的目的是证明7价肺炎球菌结合疫苗（PCV 7; Prevnar）在移植后3个月首次接种时并不劣于移植后9个月首次接种时。我们进行了一项多中心、随机、非劣效性研究，涉及来自13个欧洲血液和骨髓移植中心的158名患者，他们在清髓性干细胞移植后100天左右被随机分配接受一系列疫苗接种（间隔1个月给予3剂PCV 7），立即开始（即，移植后3个月）或6个月后（即，移植后9个月）。主要评价标准为第3剂PCV 7后1个月的应答率（抗体水平，7种血清型中的每一种均与0.15 mg/mL相似）。非劣效性界值为20%。所有患者在移植后随访24个月或直至死亡，以先发生者为准。我们发现早期接种疫苗后的应答率（79% [57例患者中的45例]）并不低于晚期接种疫苗后的应答率（82% [57例患者中的47例]）（差异为-3.5%; 90%置信区间为-15.6至8.6;不显著）。我们得出结论，干细胞移植后3个月接种PCV 7疫苗并不劣于移植后9个月接种PCV 7疫苗。由于侵袭性肺炎球菌疾病可在早期发生，我们建议在移植后3个月开始PCV 7疫苗接种系列，以确保早期预防肺炎链球菌。然而，早期疫苗接种可能仅导致短暂的应答，并且可能不如晚期疫苗接种有效地引发23价肺炎球菌多糖疫苗加强。
Background. Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation.Methods. We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at similar to 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, similar to 0.15 mg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first.Results. We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant).Conclusions. We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.