CMV Specific Cellular Immunity in Recipients of Allogeneic Bone Marrow Transplantation: Association of CMV-Specific HLA-Peptide Tetramer Binding With Cytotoxic T-Cell Function, CMV Infection and Other Clinical Events
OBJECTIVES:
- To document the quantitative characteristics of a cytomegalovirus (CMV)-specific
HLA-peptide tetramer-binding assay (TBA) for cytotoxic T lymphocytes (CTLs) in patients
who have undergone allogeneic bone marrow transplantation (BMT) or peripheral blood
stem cell transplantation (PBSCT).
- To confirm the optimal TBA conditions for CTL characterization in these patients.
- To compare the TBA results for these patients with conventional assays for CTL
functions.
- To compare CMV-specific TBA during the first 3 months after allogeneic BMT or PBSCT and
to determine whether this binding function, in either donor or recipient, is a
surrogate marker for protection from risk of CMV infection in these patients.
- To determine whether acquisition of CMV-specific TBA protects from risk for CMV disease
in patients having active CMV infection after allogeneic BMT or PBSCT.
OUTLINE: This is a multicenter study. Patients accrue initially to cohort 1 until a
sufficient number of stem cell transplantation (SCT) recipients are enrolled. Patients then
accrue to cohort 2 based on documented cytomegalovirus (CMV) infection and preemptive
treatment with ganciclovir within 90 days after SCT (patients previously accrued to cohort 1
can be accrued to cohort 2 if they develop CMV infection).
- Cohort 1: Patients undergo blood sample collection on approximately days 40, 90, 120,
150, 180, and 360 post transplantation. Samples are analyzed (to determine the
development of CMV immunity) for prevalence of CMV-specific cytotoxic T-lymphocytes
(CTL) by HLA-peptide tetramer-binding assay (TBA) pp65, with and without in vitro
stimulation (IVS). Samples collected on days 40 and 90 are also analyzed by chromium
release assay (CRA). Patients suspected of developing CMV viremia may receive
ganciclovir according to standard clinical practice.
- Cohort 2: Patients undergo blood sample collection on approximately days 90, 120, 150,
180, and 360 after SCT. Samples are analyzed by TBApp65 staining and for prospective
measurement of CMV-specific CTL functions.
All patients undergo routine clinical surveillance for CMV infection on days 21 to 100 after
SCT. CMV viral load measurements are obtained twice weekly by CMV-DNA PCR assays on blood
cells and plasma and shell-vial blood cultures. In cohort 2, CMV viral load is also
determined on days 90 (if not previously as part of cohort 1), 120, 150, 180, and 360. The
CMV infection data obtained is then compared with TBA and CTL measurements using
HLA-specific tetramers and IVS-induced cytotoxicity assays. Clinical events, such as
graft-versus-host disease, underlying disease status, and procedure-related complications
are also analyzed and correlated with TBA results.
Stromal cell cultures are obtained from marrow donors at the time of marrow harvest for use
as target cells in CTL assays. Donor saliva samples are also obtained for detection of CMV
infection by shell-vial method.
Interventional
Primary Purpose: Supportive Care
Quantitative determination of HLA-peptide tetramer-binding assay (TBA) pp65 on days 40 and 90 after stem cell transplantation, with and without in vitro stimulation
No
John A. Zaia, MD
Principal Investigator
Beckman Research Institute
United States: Federal Government
99061
NCT00716911
January 2000
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