Safety and Immunogenicity of Gardasil post stem cell transplantation

在NIH的一项研究中，患有生殖器慢性移植物抗宿主病(CGVHD)的女性中有一半在外阴症状出现后几个月内出现阴道粘连，其中三分之一发生在外阴症状出现后的几个月(Stratton，Obstet Gynecol，2007；110：1041)。一些唇部和阴道粘连的患者需要接受手术(Norian and Stratton，Obstet Gynecol，2008；112：437)。此外，全身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接受治疗的患者的阴道粘连。外用超强的类固醇和雌激素(配合阴道cGVHD扩张器)对所有外阴和部分阴道cGVHD有效。对于患有cGVHD的妇女，即使她们没有症状，也应该考虑生殖器cGVHD并进行妇科评估。 鳞状细胞癌，包括宫颈癌，是仅次于HSCT的最常见的第二种恶性肿瘤。初步报告显示，移植受者中HPV血清反应性丧失。在NIH最近的一项研究中，成年女性在HSCT后长期接受血液病细胞学检测(中位数：移植后7年；Savani和Stratton，Biol骨髓移植)。2008年9月；14：1072)。1/3有HPV相关的sIL(中位时间为sIL 51个月，范围：22-108)，其中20%为高级别sIL。需要持续免疫抑制治疗(IST)的患者风险最高(优势比OR 4.6，95%可信区间CI 1.1-16.4；P=.019)。这些异常的宫颈细胞学结果表明，HPV病似乎不是新获得的HPV病，因为许多人没有性交。HPV抗体滴度和/或T细胞免疫丧失可导致HPV病复发或重新激活，这一假设是合理的。移植后长期存活的HSCT患者中sIL的高发生率凸显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女性身上进行。妇女的生殖器cGVHD及其后遗症也将进一步描述。

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.