Studies of the Immune Response to Vaccination After Hematopoietic Stem Cell Transplantation

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.

Inclusion Criteria:

- Patients who have been treated with HSCT.

- Patients must be 5-70 years of age.

- For patients participating in Objective 3: Patients must be immunocompetent (no
active GVHD and must be off all immunosuppression)

Exclusion Criteria:

- Patients who do not wish to participate or unable to provide the necessary
blood samples required for the protocol.

- Patients with history of allergic reaction to a vaccination.

- Patient has had Guillain-Barre syndrome.

- Patients who are pregnant or become pregnant.