Vulvovaginal Graft Versus Host Disease (VV-GVHD) in Women Who Underwent Transplantation Before and After Menarche
Condition: Graft-vs-Host Disease
MeSH terms: Graft vs Host Disease
Study type: Observational

Summary: 
      The study will evaluate the prevalence and characteristics of vulvovaginal graft versus host
      disease (VV- GVHD) in patients who underwent hematopoietic stem cell transplantation (HSCT)
      as girls or adolescents and will compare the prevalence, characteristics and severity of
      VV-GVHD before and after menarche.
    

Detailed description: 
      The phenomenon of vulvovaginal graft versus host disease (VV-GVHD) following hematopoietic
      stem cell transplantation (HSCT) was first described in 1982 [Corson]. It is characterized by
      vulvovaginal inflammation, scarring, adhesions and might end with complete vaginal
      obliteration. Hematopoietic stem cells source for the allogeneic transplantation was found to
      affect the incidence of VV-GVHD: peripheral blood progenitor cells were associated with an
      incidence of 50% [Zantomio], while bone-marrow harvested cells were associated with an
      incidence of 25% [Spinelli].

      Due to the high incidence of genital GVHD and its severe consequences we established a clinic
      designated for post- transplantation patients at the Hadassah University Hospital in
      Jerusalem. In a two years follow-up we found an incidence of 54% vulvovaginal GVHD in adult
      patients who attended the clinic, similar to the incidence described in the literature.

      The data on VV-GVHD in the literature refers mainly to adult women. As gynecological
      examination and follow-up is not done routinely in girls and adolescents who are not sexually
      active, the incidence and characteristics of VV-GVHD in girls and adolescents who underwent
      HSCT is unknown.

      Methods:

      Patients who underwent allogeneic HSCT before the age of 18, who are 18 years or older at the
      time of the study and who are alive will be invited to participate in the study. Those who
      will be willing to participate will complete questionnaires and undergo physical and
      gynecological examination. At a single appointment, data will be acquired regarding: age,
      time from transplantation, current medical status, medications,hormonal status,marital
      status, sexual function and fertility (pregnancies and deliveries), assessment of sexual
      development by a pediatric endocrinologist regarding Tunner stages,data regarding possible
      vulvovaginal involvement, presence and scoring of GVHD in other organs and assessment of
      patients' well being using the FACT-BMT score.

      In order to assess engraftment and degree of chimerism, donor and host-specific DNA markers,
      using male and female amelogenine gene PCR bands and by STR-PCR assay will be done.

      Gynecological exam: in case the patient is sexually active, a complete vulvovaginal exam
      using a speculum, bimanual exam and transvaginal ultrasound will be done. In case the patient
      never had sexual intercourse, only external (vulvar) exam and abdominal ultrasound exam will
      be done.

      On exam, the following aspects will be evaluated: vulvar anatomy, vaginal examination for
      adhesions, fibrosis or stenosis. Vaginal exam will include vaginal pH measurement, saline and
      10% potassium hydroxide microscopy, evaluation for the presence of condylomas, Pap smear and
      vaginal and cervical swab for HPV.

      VV-GVHD will be defined according to clinical criteria, which include vulvovaginal anatomic
      changes, mucosal erosion and inflammation.

      Blood samples will be examined for:

      hormonal status, measurements of blood Th1/Th2 cytokines and immunoglobulins levels.

      Immune reconstitution will be evaluated by quantitative immune reconstitution done using
      peripheral blood cells. The cells will be analyzed by flow cytometry using fluorescein
      isothiocyanate antibodies for the absolute counts of various T cells sub populations, B
      cells, NK and NKT cells.

      Additional data regarding age at transplantation, menarchal status at transplantation, sexual
      activity status at time of transplantation, diagnosis, donor relation, source of cells,
      number of cells infused, protocol, conditioning regimen, immunosuppressive prophylaxis and
      occurrence of GVHD in other organs will be acquired by anamnesis and from the patients'
      files.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients who underwent allogeneic HSCT before the age of 18, who are 18 years or older at
        the time of the study and who are alive .
      
Keywords: VV GVHD; girls; adolescents; HSCT