Studies of the Immune Response to Vaccination After Hematopoietic Stem Cell Transplantation
Condition: Hematopoietic Stem Cell Transplant
Study type: Observational

Summary: 
      The purpose of this research study is to perform a serial analysis of immune function using
      blood cells and sera obtained from patients after vaccination following hematopoietic stem
      cell transplantation (HSCT). The focus of this study will be to characterize several immune
      parameters during the clinical course of HSCT and correlate these findings with the effect of
      vaccination.
    

Detailed description: 
      Hematopoietic stem cell transplantation therapy is potentially curative for many malignant
      and non-malignant hematopoietic disorders. Disease recurrence and infection remain major
      causes of morbidity and mortality following HSCT. While innate immunity (myeloid and NK cell)
      is restored relatively quickly following HSCT, a prolonged period of lymphopenia occurs in
      all patients. This delay in lymphoid reconstitution is exacerbated with age and results in
      severely dampened adaptive immune responses. In children who have received chemotherapy and
      HSCT, T cell function generally recovers within 6 to twelve months. In contrast, lymphoid
      deficiency in adults may require years, and often never recovers to pre-transplant levels.
      Much of the delay in lymphocyte recovery is thought to be due to decreased thymic T cell
      production and export and the resulting expansion of treatment resistant T cell clones.
      Peripheral expansion of T cells in a lymphopenic setting leads to a narrowing of the TCR
      repertoire and manifests as a decrease in the magnitude of response to new antigens.

      These long-lasting T cell deficiencies have been shown to play a direct role in
      post-transplant complications. There are many studies that correlate decreased T cell number
      and function (specifically CD4+ T cells) with an increase in post-transplant infections and
      relapse has been shown to be inversely proportional to T cell reconstitution following both
      autologous and allogeneic HSCT. Furthermore, this prolonged deficit in T cell function
      decreases the effectiveness of vaccination against tumour antigens and infectious diseases as
      well as other post-transplant immunotherapeutic strategies. Following HSCT, patients lose
      immunological memory not only to infectious microorganisms to which they were previously
      exposed but also bacterial and viral vaccines given prior to the HSCT , increasing the chance
      of infection post-transplant. Primary immunization requires antigenic stimulation and
      functionally mature T cells and therefore at least partial reconstitution of the T and B cell
      pools is necessary before successful reimmunization can occur.

      This study presents an opportunity to analyze, at a systems level, the responses to
      vaccination in patients who are treated with HSCT. The expected high frequency of low
      responders to vaccination will permit comparisons of gene expression and immune cell
      activation between high and low responders as measured by the rate of seroconversion and HAI
      titers. The evaluation of live VZV vaccination is essential for these objective as the
      investigators hypothesize that live vaccination will induce a more specific immune response
      than dead (ie: influenza) vaccination. This study may also generate novel hypotheses about
      the mechanistic basis for reduced responses to vaccines post HSCT.
    

Intervention name(s): Influenza vaccine; Varicella vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Influenza vaccine: Injection, post transplant; Varicella vaccine: Injection, post transplant
Other intervention name(s): flu vaccine; chicken pox vaccine
Intervention MeSH terms: Vaccines
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who have been treated with HSCT
      
Biospecimen description: 
      Serum will be collected and stored for immunologic analysis after vaccination. Samples will
      be cryopreserved. No cell lines will be created using samples procured on this protocol.
    
Keywords: blood; hematopoietic; stem; cell; transplant; vaccine; vaccination; recovery; immune; system