AGENT ORANGE AND
CHRONIC LYMPHOCYTIC LEUKEMIA
Headlines
Made, Fine Lines Ignored
Quang M. Nguyen
May
2003
On January 23, 2003, the Board on Health Promotion and Disease Prevention of
the Institute of Medicine (IOM) - a private, nonprofit institution that
provides health policy advice under a congressional charter granted to the
National Academy of Sciences (NAS) – posted a press release on the NAS website
to announce the release of the Veterans and Agent Orange: Update 2002 (VAO
2002). The VAO 2002, which was prepared by the Committee to Review the Health
Effects in Vietnam Veterans of Exposure to Herbicides (Fourth Biennial Update)
(IOM Committee), “... reassessed six studies of herbicide exposure
that provided information on chronic lymphocytic leukemia (CLL) among other
health effects. The re-examination revealed sufficient evidence of an
association between exposure to chemicals sprayed in
Immediately after the press release,
headlines were made by major international wire services such as Associated
Press (AP) and Agence France Press (AFP). Under the headline “Leukemia, Agent
Orange link found,” AP reported that “Researchers have found a link between
a type of leukemia and Vietnam soldiers exposed to herbicides like Agent
Orange, prompting the Veterans Affairs [VA] Department to announce it will
extend benefits to veterans with the illness.” (2) The “Agent Orange linked
to leukemia” from AFP reported that “Agent Orange, a defoliant used by US
forces during the Vietnam War, has been linked to a chronic form of leukemia
suffered by former soldiers, leading the US government to extend compensation
to veterans with the disease.” (3) AFP also quoted VA’s Secretary Anthony
Principi saying that “Compelling evidence has emerged within the scientific
community that exposure to herbicides such as Agent Orange is associated with
CLL... I’m exercising my legal authority to ensure the full range of VA
benefits is available to
The headline news, of course, appeared on
the internet and newspapers around the world, but they do not have any
footnotes for fine lines. The fine lines were printed on pages 283-285 of the
prepublication copy – uncorrected proof of the VAO 2002, which is also posted
on the NAS website (4). They read as follows:
Summary of Studies on CLL
In response to a request from the
Department of Veterans Affairs and because CLL shares more traits
(immunohistochemical characteristics, B-cell origin, and progression to an
acute aggressive form of NHL) with NHL than with other types of leukemia, the
committee reassessed the available epidemiologic data to determine whether CLL
merited reclassification regarding association with exposure to herbicides. The
relevant data are summarized in Table 6-50.
Six studies reported in previous
updates in which CLL was specifically investigated were reviewed. Waterhouse et
al. (1996) performed a prospective study of site-specific cancer incidence in
1,706 males and females in a rural farming community in
Two of the epidemiologic studies
reported on herbicide exposure and CLL. In a study of 1,675 white
Bertazzi et al. (2001) evaluated
lymphocytic leukemia in the 20-year follow-up of Seveso residents. No increased
risk was seen, with relative risks of 1.1 (95% CI, 0.3-4.4) and 1.0 (95% CI,
0.2-3.9) for Zone B residents and the total of Zone A and B residents,
respectively.
No relevant Vietnam-veteran
studies that specifically investigate CLL have been published since Update
2000 (IOM, 2001).
Synthesis
A reanalysis of the epidemiologic
studies indicates that farming occupation, especially where there is exposure
to the herbicides 2,4-D and 2,4,5-T, is associated
with significant risk of CLL mortality. Many more studies support the
hypothesis that herbicide exposure can contribute to NHL risk. Most cases of
CLL and NHL reflect malignant transformation of B-lymphocyte progenitor cells,
so these diseases could have a common etiology.
Conclusions
Strength of the Evidence
On the basis of its evaluation,
the committee concludes that there is sufficient evidence of an association
between exposure to at least one of the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or
cacodylic acid) and CLL.
Biologic Plausibility
No animal studies have found an
increased incidence of CLL after exposure to the chemicals of interest. A
summary of the biologic plausibility of the carcinogenicity of TCDD and the
herbicides in general is presented at the end of this chapter. Chapter 3
discusses recent toxicology studies that concern biologic plausibility.
Increased Risk of Disease Among
The limited data available on
These
fine lines were probably ignored, even by the ones who wrote or reviewed
them!
First, the IOM Committee ignored its own findings
described in the “Summary of Studies on CLL” to conclude that “... there is
sufficient evidence of an association between exposure to at least one of the
chemicals of interest (2,4-D, 2,4,5-T or its
contaminant TCDD, picloram, or cacodylic acid) and CLL.” The IOM Committee
appears to contradict itself when concluding that “No animal studies have
found an increased incidence of CLL after expose to the chemicals of interest.”
Unless the IOM Committee had additional data
and information, results from the reviewed studies are not convincing for an
association between herbicides and CLL. In fact, four of the six reviewed
studies did not provide information on herbicides exposure, and the two studies
reporting on herbicides exposure and CLL did not specify if farmers were
exposed to other chemicals other than herbicides. Chances are the farmers were
exposed because one of the two studies discussed about insecticide and animal
insecticide. One of the studies evaluates the lymphocytic leukemia in the
20-year follow-up of Seveso residents. Instead of considering the Seveso study
as the most appropriate and reliable study for its evaluation, the IOM
Committee chose to ignore it. That was probably because the Seveso study did
not show an association between exposure to dioxin and CLL.
The IOM Committee also ignored to follow its
own criteria in evaluating sufficient evidence of an association (literally in
fine lines) in Table ES-1. The criteria read “Evidence is sufficient to
conclude that there is a positive association. That is, a positive association
has been observed between herbicides and the outcome in studies in which
chance, bias, and confounding could be ruled out with reasonable confidence.”
Based on these criteria, the studies used by the IOM Committee, except the
Seveso study, should be ruled out because of confounding.
That was not the first time an IOM committee
ignored its own fine lines. “Far more ominous for public policy, the IOM
committee decided that there is a connection between Agent Orange exposure and
spina bifida, a birth defect resulting in incomplete closure of the spinal
column. The committee ignored the fact that there is no evidence for any
exposure to a male parent ever having caused a birth defect and no plausible
biological mechanism by which it could do so” (5).
Secondly, AP and AFP ignored to read the fine lines,
or ignored to obtain a pre-publication copy of the VAO 2002, when reporting
that “Researchers have found a link between a type of leukemia and Vietnam
soldiers exposed to herbicides like Agent Orange...,” and “Agent Orange,
a defoliant used by US forces during the Vietnam War, has been linked to a
chronic form of leukemia suffered by former soldiers...” There is no place
in the VAO 2002 confirming a link between CLL and
Finally, the VA ignored, if not forgot to read, the
fine lines in the IOM Committee’s conclusions regarding CLL when making its
decision to extend compensation to Vietnam veterans suffering from this form of
cancer, as a result of the IOM Committee’s findings. These fine lines are
printed on page 6 of the pre-publication copy of the VAO 2002, saying “It
should be noted that the committee is charged with reviewing the scientific
data, not with making recommendations regarding VA policy; therefore,
conclusions reported in Table ES-1 are not intended to imply or suggest policy
decisions. Furthermore, the conclusions are related to association between
exposure to chemicals and health outcomes in human populations, not to the
likelihood that any individual’s health problem is associated with or caused by
the herbicides in question,” and on page 285, saying “The limited data
available on Vietnam veterans do not suggest that they are at increased risk
for CLL.”
In reality, “...no one knows how many
Vietnam vets have been diagnosed with the disease,... and some veterans’
advocates wonder if there really are any vets suffering from CLL” (6).
There is possibly none because “... I’ve been doing this for 14 years and I
do not recall ever having a veteran come to me and say ‘I have chronic lymphocytic
leukemia.’ Ever,” says Phil Kraft (6). Mr. Kraft is a program director of
the National Veterans Services Fund, a nonprofit organization providing
counseling and other services for
Quang M. Nguyen.
REFERENCES
1.
The
National Academies. January 23, 2003. “New Report Supports Association Between
Agent Orange and One Form of Chronic Leukemia.” Office of News and Public
Information. http://www4.nationalacademies.org/news.nsf
2.
Associated
Press.
3.
Agence
4.
http://books.nap.edu/books/030908616/html/1.html
5.
Michael
Gough.
6.
Amanda
Gardner.