Safety and Immunogenicity of Gardasil post stem cell transplantation

在NIH研究中，患有生殖器慢性移植物抗宿主病（cGVHD）的女性中有一半具有阴道粘连，其中三分之一在外阴症状后数月发展（Stratton，Obstet Gynecol，2007;110：1041）。有些阴唇和阴道粘连需要手术（Norian和Stratton，妇产科，2008;112：437）。 此外，全身性免疫抑制在预防或治疗生殖器cGVHD方面无效。 雌激素环改善了所有治疗患者的阴道粘连。局部超强效类固醇和雌激素（阴道cGVHD扩张剂）可有效治疗所有外阴和部分阴道cGVHD。应考虑生殖器cGVHD，并对cGVHD女性进行妇科评估，即使她们无症状。 鳞状细胞癌，包括宫颈癌，是HSCT后最常见的第二种恶性肿瘤。 初步报告表明移植受者中HPV血清反应性丧失。 在最近的一项NIH研究中，对成年女性进行了前瞻性随访，在HSCT后长期进行宫颈细胞学检查以检测血液恶性肿瘤（中位数：移植后7年; Savani和Stratton，Biol Blood Marrow Transplant. 2008年9月;14：1072）。三分之一有HPV相关的SIL（SIL的中位时间为51个月，范围：22-108），包括20%的高级别SIL。需要继续免疫抑制治疗（IST）的患者风险最高（比值比OR 4.6，95%置信区间CI 1.1-16.4; P = 0.019）。这些异常的宫颈细胞学结果代表HPV疾病，似乎不是新获得的HPV疾病，因为许多人没有性交。可以合理地假设，对HPV的抗体滴度和/或T细胞免疫力的丧失可能导致HPV疾病的复发或再激活。长期HSCT存活者SIL的高发病率强调了移植后妇科评估以及潜在预防策略评估的重要性。 明年，这项临床研究将在干细胞移植后的妇女中进行。女性生殖器cGVHD及其后遗症也将进一步表征。

In a NIH study, half of the women with genital chronic graft-versus-host-disease (cGVHD) had vaginal adhesions with one-third of these developing months after vulvar symptoms (Stratton, Obstet Gynecol, 2007;110:1041). Some with labial and vaginal adhesions have required surgery (Norian and Stratton, Obstet Gynecol, 2008;112:437). Furthermore, systemic immunosuppression is ineffective in preventing or treating genital cGVHD. An estrogen ring improved vaginal synechiae in all treated patients. Topical superpotent steroids and estrogen (with dilators for vaginal cGVHD) were effective in treating all vulvar and some vaginal cGVHD. Genital cGVHD should be considered and gynecologic assessment performed in women with cGVHD, even if they are asymptomatic. Squamous cell cancers, which include cervical cancer, are the most common second malignancy after HSCT. Preliminary reports indicate a loss of HPV seroreactivity among transplant recipients. In a recent NIH study, adult females were followed prospectively with cervical cytology testing long-term after HSCT for hematological malignancies (median: 7 years post-transplant; Savani and Stratton, Biol Blood Marrow Transplant. 2008 Sep;14:1072). One-third had HPV-related SIL (median time to SIL 51 months, range: 22-108) including high-grade SIL in 20%. Patients requiring continued ImmunoSuppressive Therapy (IST) had the highest risk (odds ratio OR 4.6, 95% confidence interval CI 1.1-16.4; P = .019). These abnormal cervical cytology results represent HPV disease that does not appear to be newly acquired HPV disease as many are not having intercourse. It is reasonable to hypothesize that a loss of antibody titers and/or T cell immunity to HPV can cause recurrence or reactivation of HPV disease. This high incidence of SIL in long-term HSCT survivors underscores the importance of gynecologic assessment after transplantation as well as the assessment of potential preventative strategies. In the next year, this clinical study will be conducted in women post stem cell transplantation. Genital cGVHD and its sequelae in women will also be further characterized.