Pao Mary, Papadopoulos Esperanza B, Chou Joanne, Glenn Heller, Castro-Malaspina Hugo, Jakubowski Ann A, Kernan Nancy A, Perales Miguel A, Prokop Susan, Scaradavou Andromachi, vanDenBrink Marcel R, Young James W, O'Reilly Richard J, Small Trudy N
Memorial Sloan Kettering, New York, New York.
Memorial Sloan Kettering, New York, New York.
Biol Blood Marrow Transplant. 2008 Sep;14(9):1022-1030. doi: 10.1016/j.bbmt.2008.06.012.
Young children and allogeneic hematopoietic cell transplantation (HCT) recipients respond poorly to polysaccharide antigens, rendering them susceptible to severe infections because of encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults, P < .001). Overall response to HIB was 86%, including 77% of PNCRM7 nonresponders. Although PNCRM7 response was adversely affected by older age (P < .001), individuals > or =50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multicenter trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted.
幼儿和异基因造血细胞移植(HCT)受者对多糖抗原反应不佳,由于荚膜细菌,他们易受严重感染。本研究评估了127例HCT患者(中位年龄23.0岁)接种PNCRM7和流感嗜血杆菌(HIB)结合疫苗后的反应,这两种结合疫苗在健康儿童中具有高度免疫原性。接种疫苗的中位时间为HCT后1.1年。62%的患者对PNCRM7有反应(51名儿童中的45名,76名成人中的34名,P <.001)。对HIB的总体反应率为86%,其中包括77%对PNCRM7无反应者。尽管PNCRM7反应受到年龄较大的不利影响(P <.001),但如果在获得特定的最低免疫能力里程碑后接种疫苗,即CD4>200/μL、IgG>500 mg/dL、PHA在正常下限的60%以内,≥50岁的个体反应明显更好(19名中的11名与8名中的0名,P <.006)。在慢性移植物抗宿主病(cGVHD)有限的患者中也观察到类似趋势。在所有患者中,循环CD4(+)CD45RA细胞水平较高与PNCRM7反应改善相关。这些数据表明,PNCRM7在异基因HCT患者中具有免疫原性,包括老年人,但表明HCT后固定间隔接种疫苗,无论免疫能力如何,可能会限制其有效性。有必要进行前瞻性、多中心试验,评估接种该疫苗的最佳策略及其对移植后肺炎球菌感染的影响。