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

Hematopoietic Stem Cell Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01581164
• Other study ID #: UCSF Protocol No. 112526
• Status: Completed
• Phase: N/A
• First received: April 16, 2012
• Last updated: May 7, 2015
• Start date: December 2011
• Est. completion date: December 2014

Study information

• Verified date: May 2015
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 70 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant

Intervention

Biological:
• Influenza vaccine
Influenza vaccine: Injection, post transplant
• Varicella vaccine
Varicella vaccine: Injection, post transplant

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of Immune response at Day 90 post vaccination.	Participants will have blood drawn at baseline to Day 90 post vaccinations following hematopoietic stem cell transplantation. Average study participation is 1-3 years post transplant.	Participants will have blood drawn at baseline and on Days 1, 7, 10, 28, and 90 post vaccinations following hematopoietic stem cell transplantation. Average study participation is 1-3 years post transplant.	No
Secondary	Immune response		Participants will have blood drawn at 1 month intervals post hematopoietic stem cell transplantation . Average study participation is 1-3 years post transplant.	No
Secondary	Immune response		Blood will drawn at baseline and Days 1, 7, 10, 28, and 90 post vaccination. Participants will receive the vaccine, 12-28 months post hematopoietic stem cell transplantation.	No