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Terrace Garden Inn
Atlanta, Georgia
June 14-15, 1995
*
Hosted by the National Center for Environmental Health
Centers for Disease Control and Prevention
Chairpersons
Gerald E. Marti, M.D., Ph.D.
Senior Investigator
Center for Biologics Evaluation and Research
Food and Drug Administration
Bldng 29, Room 502
8800 Rockville Pike
Bethesda, MD 20892
301-496-9559 FAX: 301-496-4684
Internet: gemarti@helix.nih.gov
Robert F. Vogt, Jr., Ph.D.
Research Chemist
National Center for Environmental Health
Centers for Disease Control and Prevention
Mailstop F19
Atlanta, GA 30333
404-488-7971 FAX: 404-488-4609
Internet: RFV1@CEHEHL1.EM.CDC.GOV
Preliminary Agenda
Objective
=========
Describe specific laboratory and epidemiologic methods for
addressing the following questions:
1) What is the age-related prevalence, natural history
and differential diagnosis of B-cell
lymphoproliferative dyscrasias detectable in
peripheral blood?
2) What genetic and environmental risk factors
contribute to developing such B-cell dyscrasias and
associated diseases?
Schedule
========
Wednesday, June 14
8:15 AM Introductions and Overview of Workshop (R. Vogt)
9:00 AM Immunobiology of B-cells and CLL (G. Marti and
others)
11:00 AM Risk Factors and Epidemiologic Considerations
(R. Vogt and others)
11:45 AM RECESS and LUNCH
1:00 PM Breakout sessions:
1) Immunobiology & Laboratory Considerations
2) Epidemiology & Field Considerations
5:00 PM RECESS and DINNER
7:30 PM Informal review of breakout sessions
Research opportunities in planned or existing
studies
Thursday, June 15
8:00 AM Writing Block: Responses to Pre-Workshop
Questions and Newly-Raised Issues
11:00 AM Public Health Issues:
Informed Consent
Ethical Considerations
Genetic Screening
Tissue Banking
Participant Counseling
Longitudinal Studies/VA Medical Centers
Support for Clinical Evaluation and Treatment of
Study Participants
1:00 PM ADJOURN FORMAL SESSIONS
2:00 PM (Optional) Review and Assimilation of Material
by Workshop Organizers and Participants
PHS Agency Participants
=======================
Agency for Toxic Substances and Disease Registry (ATSDR)
National Center for Environmental Health, CDC
Center for Biologics Evaluation and Research, FDA
National Cancer Institute, NIH
National Institute on Aging, NIH
National Institute of Environmental Health Science, NIH
Background
==========
Over the last 5 years, ATSDR and CDC have analyzed
peripheral blood samples from over 6000 individuals for
immune biomarkers in epidemiologic studies conducted at
Superfund sites. A standardized panel of immune tests was
used in 10 different studies to characterize the occurrence
of abnormal immune parameters in people living near
hazardous waste sites and in demographically-matched
comparison groups. Laboratory analysis included lymphocyte
phenotyping to identify the major lineages (T-cells,
B-cells, NK-cells) and functional sub-populations
discriminated by CD4 and CD8, and, in some cases, CD5 and
HLA-Dr. Serum immunoglobulin levels were also measured.
The most striking finding to date has been the appearance
in 11 samples of B-cell phenotypes suggestive of chronic
lymphocytic leukemia (CLL). While one sample came from a
previously-diagnosed CLL case, the remainder were
apparently sub-clinical and were not detected by simple
blood counts. Because the ultimate relationship of these
phenotypes to disease is uncertain, we refer to them as
B-cell lymphoproliferative dyscrasias. The overall
detection rate of these phenotypes was 104-fold greater
than the age-adjusted incidence of CLL, and the
age-adjusted detection rate was almost twice as high in the
Superfund target populations as in the comparison groups.
Discussions with other investigators and clinicians has
reinforced the idea that sub-clinical B-cell
lymphoproliferative dyscrasias may be identified much more
commonly than generally recognized. The epidemiology
(incidence, prevalence, risk factors, and natural history)
of these conditions is unknown. However, several
epidemiologic studies have suggested that environmental
exposures, including industrial chemicals and
electromagnetic fields, may increase the risk of B-cell
immunoproliferative diseases including CLL, non-Hodgkins
lymphoma, and multiple myeloma. Since B-cells are
inherently genomically unstable, they may be particularly
sensitive targets to environmentally-induced damage and
serve as sentinels for such exposures. This workshop has
been convened to plan studies which would test this
hypothesis.
Gerald E. Marti
Flow and Image Cytometry Section
Laboratory of Medical and Molecular Genetics
Division of Cell and Gene Therapies
CBER FDA NIH Bdg 29 Rm 502
8800 Raockville Pike
Bethesda,MD 20892
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