Gardasil Vaccination in Post Stem Cell Transplant Patients

HPV associated genital dysplasia is a complication following hematopoietic allogeneic stem cell transplantation (HSCT). In a recent study from this institution, one third of female transplant recipients had HPV related genital tract dysplasia. The quadrivalent human papillomavirus virus (HPV) (types 6, 11, 16, 18) vaccine (Gardasil ) is now approved for use in females aged 9-26 for the prevention of cervical cancer and, more recently, vulvar and vaginal cancer. In this study, Gardasil will be used in females age 18 years to 50 at least 90 days post stem cell transplant in two study cohorts to determine its safety and immunogenicity in this population, as a first step to reduce post-transplant HPV-related co-morbidity, genital dysplasia and malignancy. The two study cohorts will both be post transplant; one off of immunosuppression (n=24), and one on immunosuppression (n=24). Gardasil will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. The primary objectives of this study are to determine the safety and immunogenicity of Gardasil in female allogeneic HSCT recipients. A cohort of healthy subjects will also be vaccinated (n=24) and will serve as a control. Immunogenicity studies characterizing the CD4 and CD8 T- cell response, change in antibody titer and cytokine response from baseline to months seven and twelve will be compared in the three cohorts. Additionally, genital exams will be performed to monitor for HPV. Secondary endpoints will characterize sexual function post-transplant and vulvar/vaginal graft-versus-host disease (GVHD). When available, healthy female stem cell donors corresponding to enrolled vaccine recipients will be enrolled (n=10) as part of the healthy cohort and vaccinated to determine whether there are differences in HPV vaccine immunogenicity in a subset of donors and their respective allogeneic, HSCT female recipients.

As stem cell transplant becomes more applicable to the general population with newer transplant techniques allowing for a larger donor pool and as survival improves, problems associated with long term survivorship such as genital dysplasia, will become more prevalent. Vaccine therapy to prevent or eradicate this disease is needed.

• INCLUSION CRITERIA:

Female stem cell transplant recipient at least 90 days post stem cell transplant

OR

Female stem cell transplant recipient at least 90 days post HSCT and on immunosuppression

OR

The matched female stem cell transplant donor for an included stem cell transplant recipient

OR

Healthy female subject

Age greater than or equal to 18 years and less than or equal to 50 years

Exclusion criteria

Vaccine Recipient:

Obvious HPV condyloma or obvious severe dysplasia (greater than or equal to CIN II) warranting treatment

History of severe adverse reaction to any components (yeast, eggs, monosodium glutamate or neomycin) of the quadrivalent HPV vaccine.

Untreated or persistent life-threatening infections not controlled by current treatment

Uncontrolled chronic GVHD i.e. highly active eGVHD requiring immediate intervention

Pregnant or breast feeding or unwilling to be abstinent or practice effective contraception during the study period (note: patients who have been rendered infertile with total body irradiation are eligible)

Enrollment in another vaccine clinical trial during the study period

Enrollment of healthy volunteer in a drug clinical trial during the study period

Inability to comprehend the investigational nature of the study and provide informed consent<TAB>

Prior Gardasil or other HPV vaccination

Persistent or recurrent malignancy