Safety and Immunogenicity of Gardasil post stem cell transplantation

在美国国立卫生研究院的一项研究中，一半患有生殖器慢性移植物抗宿主病（cGVHD）的女性有阴道粘连，其中三分之一在外阴症状出现几个月后发生（Stratton, Obstet Gynecol, 2007;110:1041）。一些唇部和阴道粘连的患者需要手术治疗（Norian and Stratton, journal of obstetrics Gynecol, 2008;112:437）。此外，全身免疫抑制对预防或治疗生殖器cGVHD无效。雌激素环改善了所有治疗患者的阴道粘连。局部强效类固醇和雌激素（伴阴道cGVHD扩张剂）治疗所有外阴和部分阴道cGVHD均有效。应考虑生殖器cGVHD，并对患有cGVHD的女性进行妇科评估，即使她们没有症状。

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.