August 19, 2005 

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): RECONSIDERATION OF 

EXCLUSION FROM ELIGIBILITY FOR COMPENSATION UNDER EEOICPA 

I. Background 

The Energy Employees Occupational Illness Compensation Program Act of 2000 

(EEOICPA) provides a lump sum payment of $150,000 plus medical benefits to any 

covered former U.S. nuclear weapons worker diagnosed with cancer, if that cancer was 

judged to be “as least as likely as not” (a 50% or greater probability) caused by 

occupational exposure to ionizing radiation. The Department of Health and Human 

Services (HHS) is charged with developing and updating, as needed, the scientific 

guidelines for assessing eligibility for compensation. The Office of Compensation 

Analysis and Support (OCAS) of the National Institute for Occupational Safety and 

Health (NIOSH) performs this function for HHS. 

Each EEOICPA cancer claim is individually evaluated according to the claimant’s 

radiation dose, type of cancer, and other relevant factors by means of a computerized set 

of quantitative risk assessment models. These computerized models provide “probability 

of causation” estimates for radiation-exposed individuals. Probability of causation is 

defined as the likelihood, expressed as a percentage, that a worker’s cancer was caused 

by occupational exposure to ionizing radiation. 

The amount and type of radiation exposure incurred by a claimant is established by a 

process called “dose reconstruction.” Dose reconstruction consists of systematic research 

and analysis leading to a quantitative estimate of radiation exposure. The reconstructed 

radiation dose, type of cancer, and related factors determine probability of causation and, 

in turn, the success or failure of a claim. A probability of causation of 50% or greater 

means that the cancer was at least as likely as not induced by radiation and, thus, that it 

merits compensation. 

II. Treatment of chronic lymphocytic leukemia under EEOICPA 

Chronic lymphocytic leukemia (CLL) is currently regarded as a non-radiogenic cancer 

under the regulations (DHHS, 2002) that established the guidelines for determining 

probability of causation under EEOICPA. CLL is the only type of cancer assigned, a 

priori, a probability of causation of zero. 

NIOSH excluded CLL from coverage primarily because no elevation in CLL incidence 

had been observed among the Japanese World War II atomic bomb survivors, the data 

source from which most cancer risk models used under EEOICPA were derived. In 

addition, in NIOSH’s judgment, other epidemiological evidence available at the time the 

guidelines were promulgated did not convincingly demonstrate an association between 
2

ionizing radiation and increased risk of CLL. Moreover, the National Cancer Institute 

(NCI) had specifically excluded CLL from radiation risk calculations in a set of radioepidemiologic tables used in adjudicating cancer claims filed by radiation-exposed 

military veterans. (NCI, 2000.) In addition, NIOSH observed that CLL was not covered 

by any other radiation compensation program. 

III. Why NIOSH is reconsidering CLL 

Although CLL was designated non-radiogenic for compensation purposes, other types of 

cancer lacking compelling evidence of radiogenicity (e.g., prostate cancer, nonHodgkin’s lymphoma, hairy cell leukemia, etc.) were not excluded from eligibility for 

compensation. For those cancers, NIOSH judged that the evidence, even though in some 

instances marginal, was nonetheless sufficient to err on the side of eligibility. Further, 

NIOSH’s cancer designations were consistent with NCI’s position. NIOSH noted at the 

time, however, that the designation of CLL as non-radiogenic would be revisited in the 

future (NIOSH, 2002.) In the interim, this perceived disparity in the treatment of cancers 

with questionable evidence of radiogenicity has generated concern among EEOICPA 

claimants and other stakeholders. 

Proponents of including CLL for compensation have advanced the following arguments: 

1. There are hundreds of different types and sub-types of cancer, including many 

with sparse evidence of radiogenicity, yet only CLL is specifically excluded from 

compensation under EEOICPA. It is not plausible that CLL could be the only 

type of cancer that can not possibly be induced by radiation. Moreover, there is 

no scientific evidence that convincingly demonstrates it is non-radiogenic.

NIOSH comment: NIOSH did not assert that evidence proves CLL is nonradiogenic, only that evidence had not supported the case for radiogenicity. 

2. A major reason for excluding CLL was the apparent absence of excess risk 

among the Japanese A-bomb survivor cohort. However, the reported incidence of 

CLL varies widely among populations throughout the world. In fact, CLL is rare 

among the Japanese population and extremely rare among Japanese females (the 

majority of the A-bomb cohort) prior to age 70. Thus, the ability to detect excess 

CLL risk due to radiation exposure from atomic bombs is poor. 

NIOSH comment: NIOSH agrees that the statistical power to detect excess CLL 

risk among the Japanese survivor cohort was limited. 

3. Hairy cell leukemia (HCL) is a slowly progressing lymphocytic leukemia. 

Because its symptoms are similar to CLL, it has sometimes been misdiagnosed as 

CLL. In fact, it has been regarded by some as a sub-type of CLL. Misdiagnoses 

of cancers of the blood and bone marrow were more common when many 

EEOICPA claimants were diagnosed with cancer, before improvements in 
3

diagnostic techniques had been achieved. Thus, it’s likely that medical records 

for some claimants may contain inaccurate diagnoses. Despite the similarities 

between HCL and CLL and the diagnostic problems associated with those 

similarities, HCL is eligible for compensation under EEOICPA, but CLL is not. 

The disparity in treatment of these diseases is neither fair nor justified. 

NIOSH comment: NIOSH generally defers to NCI for expertise in the 

classification of cancers, and NCI has consistently regarded HCL and CLL as 

separate diseases. On the other hand, this distinction is not universal; for 

example, the United Kingdom’s radiation compensation program excludes both 

CLL and HCL from compensation eligibility. 

4. NIOSH convened a public meeting in Washington, DC in July 2004 to seek 

input on gaps in CLL research. That meeting featured a panel discussion of 

experts from the fields of epidemiology, medicine, radiobiology, and related 

health sciences. A consensus seemed to emerge among this NIOSH-convened 

panel that scientific evidence is inconclusive with respect to CLL’s etiology and to 

its association with ionizing radiation. The intent of EEOICPA, and the often 

stated intention of NIOSH in carrying out its mandate under EEOICPA, is to err 

on the side of the claimant whenever scientific evidence is lacking. The arbitrary 

exclusion of CLL, without regard to an individual’s degree of radiation exposure 

or to the stochastic nature of cancer risk, is clearly contrary to that intent. 

NIOSH comment: The public meeting referred to above was convened on July 21, 

2004 by NIOSH’s Health-Related Energy Research Branch (HERB) as part of an 

ongoing effort to investigate the possible relationship between ionizing radiation 

and CLL. HERB has not yet published a report of that meeting. However, 

NIOSH/OCAS reaffirms its commitment to err on the side of the claimant 

whenever the state of scientific knowledge is lacking. 

NIOSH is sensitive to the perception of disparate categorization of radiogenic cancers. 

Moreover, as noted earlier, it was stated when EEOICPA program guidelines were first 

published in 2002 that CLL would be revisited at a later date. Thus, NIOSH/OCAS 

determined in 2004 that it would be appropriate to reconsider the 2002 exclusion of CLL 

from eligibility for compensation. 

IV. Solicitation of expert opinion 

As part of the process of reconsidering CLL for EEOICPA compensation purposes, 

NIOSH/OCAS in October-November 2004 solicited the independent opinions of five 

experts otherwise unaffiliated with NIOSH, each of whom was selected based on his or 

her experience and expertise in the field of epidemiology, medicine, and/or radiation 

carcinogenesis. 

Each expert was asked, separately, to (1) review a document outlining the CLL issue as it 

pertains to EEOICPA (NIOSH/OCAS, 2004), (2) respond in writing to the question 
4

reprinted below, and (3) provide a rationale for his or her conclusion. In addition, each 

expert was provided with the program guidelines for determining compensation (DHHS, 

2002) and a draft bibliography of relevant CLL literature, the latter prepared by NIOSH’s 

Health-related Energy Research Branch (NIOSH/HERB, 2004.) However, reviewers 

were invited to base their professional conclusions on any combination of personal 

expertise, NIOSH-provided documents, or reference materials of their own choosing. 

The question posed to each contributor was: “In your expert judgment, is the evidence of 

an association, or lack thereof, between radiation exposure and the risk of developing 

CLL sufficient to continue to regard CLL as a non-radiogenic cancer and to continue to 

exclude it, a priori, from eligibility for compensation under EEOICPA?” 

Note that the above question was intentionally framed within the narrow context of 

compensation policy. NIOSH/OCAS does not seek nor presume to resolve the scientific 

controversy surrounding CLL and radiation, nor should any policy decision that may 

arise from the current reconsideration of CLL for compensation purposes be construed as 

NIOSH’s position on CLL’s radiogenic properties or lack thereof. 

Given the above caveat, expert opinions were obtained from five individuals. They are 

listed below in alphabetical order (titles and affiliations provided for information only), 

followed by their respective conclusions and (capsule) rationales. 

1. John D. Boice, Jr., ScD

Scientific Director 

International Epidemiology Institute 

Rockville, MD 

& 

Professor of Medicine 

Vanderbilt University School of Medicine 

Nashville, TN 

Boice’s conclusion: “...CLL should not be considered a radiation-inducible cancer.” 

Rationale given: (Excerpted) “The body of scientific evidence indicates that CLL is not 

caused by exposure to ionizing radiation at any level of dose. Not one of the major 

epidemiologic studies of (exposed patients or workers) has reported a statistically 

significant increase in CLL. Authoritative committees...have concluded that CLL is not 

caused by ionizing radiation. CLL appears etiologically and clinically a lymphoma and 

differs from the other forms of leukemia. Lymphomas have also not been convincingly 

linked to ionizing radiation. In the same epidemiologic studies that find significant 

increases in myeloid leukemia, no increases in CLL are found despite CLL being the 

most frequent leukemia among adult Western populations. The etiologic factors that 

cause CLL are not well defined but are different from those factors that cause other forms 

of leukemia. (Note: Dr. Boice lists benzene, cigarette smoking, and alkylating agents as 

examples of agents that cause myeloid leukemia but not CLL.) Thus based on 

epidemiologic studies of radiation finding no evidence for an association with CLL, 

coupled with the etiologic and clinical differences between CLL and the other forms of 
5

leukemia that are caused by radiation, CLL should not be considered a radiationinducible cancer.” (Boice, 2005) 

2. Mark A. Crowther, MD, MSc, FRCPC 

Associate Professor of Medicine 

Hematology Residency Program Director & Head of Service, Hematology 

McMaster University & St. Joseph’s Hospital 

Hamilton, Ontario, CA 

Crowther’s conclusion: “...the available evidence is insufficient to rule out an 

association between ionizing radiation and CLL; in this case my interpretation of 

the current standards is that compensation should be provided.” 

Rationale given: (Paraphrased/excerpted) Although an association between radiation and 

CLL has not been established through epidemiology, this can be explained by the low 

rates of CLL among Asian populations, the misclassification of hematological cancers 

prior to improved diagnostic techniques, the relatively short follow-up periods of most 

studies, and a lack of randomized clinical trials. “CLL is clearly not different from other 

forms of cancer...it is caused by a deficit of programmed cell death, rather than excess 

proliferation. However, this characteristic is shared with other cancers currently 

considered compensable. CLL is associated with (and likely due to) specific genetic 

mutations...specific genetic mutations are one of the consequences of exposure to 

radiation.” Given the lack of compelling evidence that CLL cannot be caused by 

radiation, it should be eligible for compensation. (Crowther, 2004) 

3. David M. Ozonoff, MD, MPH 

Professor of Environmental Health 

Boston University School of Public Health 

Boston, MA 

Ozonoff’s conclusion: “In summary, my expert opinion supports including CLL as a 

radiogenic cancer and against the continuing, and it seems to me, arbitrary practice 

of exclusion.” 

Rationale given: (Excerpted) “The arguments for continued exclusion are not only weak, 

but lacking in foundation. Considering that all blood cells come from a common 

progenitor stem cell it has always seemed plausible to me that any cancer of the blood 

system could be radiation related. This is now generally accepted as true for benzene, 

which also affects progenitor stem cells. ... We tend to forget that the four ‘forms’ of 

leukemia (ALL, AML, CML and CLL) are designations made on clinical grounds and are 

related to prognosis and management rather than etiology. Indeed if one wanted to 

employ cell surface markers, there could be hundreds or even thousands of ‘different’ 

types of leukemia. ... Thus while the type of leukemia is very important if one wants to 

treat the disease it is incorrect to assume this is related to etiology. Just as the difference 

between a fracture of the thigh bone and the wrist bone is extremely important for 

treatment and management of a fracture, it says nothing about the etiology of either.” 

(Ozonoff, 2004) 
6

4. David B. Richardson, PhD 

Assistant Professor of Epidemiology 

University of North Carolina School of Public Health 

Chapel Hill, NC 

Richardson’s conclusion: “Available scientific evidence does not provide sufficient 

grounds for continuing to regard chronic lymphocytic leukemia (CLL) as a nonradiogenic form of cancer.” 

Rationale given: (Excerpted/paraphrased) “...conclusions regarding ionizing radiation as 

a cause of human cancer are based upon a synthesis of evidence from molecular and 

cytogenetic research, experimental studies in radiobiology, epidemiology, and theoretical 

work on cancer causation.” With regard to CLL pathogenesis, NIOSH appears to have 

granted insufficient weight to mechanistic evidence and too much weight to observational 

epidemiology. Epidemiological evidence for radiation-induced CLL is limited due to 

factors such as relatively long latency and unreliable case ascertainment. “This is an 

inappropriate weighting of evidence for the evaluation of whether ionizing radiation 

exposure is a cause of CLL. ...the scientific evidence pertaining to the molecular 

mechanisms of CLL induction weighs heavily towards the conclusion that CLL is similar 

to other hematological malignancies... The weight of this scientific evidence is in support 

of the conclusion that the somatic mutations that contribute to the genesis of CLL can be 

produced by ionizing radiation exposure. ... Available scientific evidence suggests that 

CLL incidence will be increased by exposure to ionizing radiation. Scientific evidence 

does not provide a sufficient basis for regarding CLL as non-radiogenic.” (Richardson, 

2004) 

5. Lydia B. Zablotska, MD, PhD 

Assistant Professor of Clinical Epidemiology 

Columbia University School of Public Health 

New York, NY 

Zablotska’s conclusion: “...from an epidemiological point of view it is not possible 

to prove that there is no risk of CLL due to occupational radiation exposure. It is 

only possible to say that currently we do not have solid scientific evidence to say that 

CLL is radiogenic.” 

Rationale given: (Excerpted) “...even after extended follow-up of the cohorts which were 

used by the BEIR V Committee as the basis for leukemia risk models, there appears to be 

no association between exposures to ionizing radiation and chronic lymphocytic leukemia 

either in Asian or Western populations. ... From the scientific point of view, this 

(epidemiological) evidence could be interpreted as the absence of a convincing 

association between radiation exposure and subsequent CLL. ... CLL remains one of the 

most controversial issues in radiation epidemiology. Though in the past it was thought to 

be definitely non-radiogenic, recent discoveries, particularly from genetic and molecular 

studies, provide evidence that lymphatic cancers may differ to a great degree from other 

types of leukemia. If risks are present, they are probably so small as to render them 

virtually undetectable in individual studies under currently available scientific 

epidemiological methods.” (Zablotska, 2004) 
7

V. Summary

Boice argues strongly that little if any evidence supports the contention that CLL can be 

induced by ionizing radiation, even at minimal exposure levels, a position supported by 

authoritative committees. In fact, numerous epidemiologic studies of varied populations 

have consistently demonstrated a lack of association between CLL and ionizing radiation. 

Further, he notes that significant differences exist between CLL and other types of 

leukemia. CLL is etiologically and clinically more akin to a lymphoma, and evidence 

associating lymphomas with ionizing radiation is weak at best. Finally, the fact that other 

types of cancers weakly (if at all) associated with radiation are (mistakenly) eligible for 

compensation does not justify adding CLL. CLL presents the weakest case for radiation 

induction of all cancers. 

Zablotska seems to concur with Boice on most points, but she also notes that recent 

genetic and molecular evidence casts some doubt on the traditional notion that CLL is 

non-radiogenic. While thus conceding the possibility that CLL may be induced by 

radiation, she adds that the risk, if any, would likely be so small as to be undetectable by 

epidemiological studies. Her conclusion is much more cautious than Boice’s. While 

evidence for an association between ionizing radiation and CLL is weak, it cannot be 

demonstrated that the risk is zero. 

Crowther, Ozonoff, and Richardson maintain that it is scientifically illogical to presume 

that CLL is not radiogenic, each citing various (and often similar) biologic and 

mechanistic constructs in support of radiation induction. In fact, they maintain, cellular 

and other non-epidemiologic evidence tends to support the case for radiation induction; 

thus, it is much more plausible to assume that CLL, like other forms of cancer, is 

radiogenic. All agree that available scientific evidence does not support the continued 

exclusion of CLL from compensation. Moreover, given that NIOSH’s stated policy is to 

err on the side of claimants if scientific evidence is inconclusive, it is thus arbitrary, 

inconsistent, and unfair to regard CLL as non-radiogenic. 

VI. Recommendation 

Three of the five expert consultants (Crowther, Ozonoff, Richardson) maintain 

unequivocally that CLL is radiogenic and that it should not be excluded from 

compensation. Only one (Boice) of the five experts concludes that CLL should 

absolutely not be regarded as a radiation-inducible cancer under EEOICPA. Another 

(Zablotska) takes a position that could be categorized as cautious. 

The issue hinges on how NIOSH should proceed in the absence of conclusive scientific 

evidence. Although epidemiological evidence appears to offer little support for 

concluding that CLL is a radiogenic cancer, a small positive risk cannot be excluded. 

Furthermore, objections have been raised with regard to the power and methodology used 
8

to address CLL in past epidemiologic studies. The biological, mechanistic evidence 

lends somewhat more support for the plausibility of CLL as a radiogenic cancer, but is far 

from conclusive. The differences in the expert opinions solicited by NIOSH appear to 

stem from the relative weight given to the epidemiologic and mechanistic evidence. 

Given the direction, as set forth in EEOICPA, to side with the claimants in the face of 

scientific uncertainty, NIOSH proposes to (1) now regard CLL as a possibly radiogenic 

cancer for purposes of compensation eligibility and to cease excluding it from 

compensation under EEOICPA, and (2) to create a new risk model for CLL, 

incorporating risk coefficients consistent with those assigned to other cancer risk models 

of similarly weak evidence for radiation induction. 

NIOSH notes that this action should be regarded as a policy decision which applies only 

to compensation eligibility under EEOICPA. It is not intended to apply, nor should it be 

construed as applying, to other compensation programs or to regulatory issues outside of 

EEOICPA, nor should it be interpreted as official NIOSH policy regarding the radiogenic 

nature or lack thereof of chronic lymphocytic leukemia. 

VII. References

Boice JD. Reconsideration of chronic lymphocytic leukemia for purposes of 

compensation. Report submitted to NIOSH, January 2005 

Crowther MA. (untitled) CLL report submitted to NIOSH, November 2004 

Department of Health and Human Services. 42 CFR Parts 81 and 82: Guidelines for 

Determining the Probability of Causation and Methods for Radiation Dose 

Reconstruction under the Employees Occupational Illness Compensation Program Act of 

2000; Final Rules, May 2002 

National Cancer Institute (NCI). Draft Report of the NCI-CDC Working Group to Revise 

the 1985 NIH Radioepidemiological Tables. May 2000 

National Institute for Occupational Safety and Health (NIOSH). NIOSH-Interactive 

RadioEpidemiological Program (NIOSH-IREP) Technical Documentation, June 2002 

National Institute for Occupational Safety and Health (NIOSH)/Health-Related Energy 

Research Branch (HERB). Chronic Lymphocytic Leukemia: Annotated Bibliography 

(Draft), July 2004 

National Institute for Occupational Safety and Health (NIOSH)/Office of Compensation 

Analysis and Support (OCAS). Chronic Lymphocytic Leukemia: Reconsideration of 

Exclusion from Eligibility for Compensation under EEOICPA, October 2004 

Ozonoff DM. Reconsideration of CLL. Report submitted to NIOSH, December 2004 
9

Richardson DB. Chronic Lymphocytic Leukemia: Reconsideration of Exclusion from 

Eligibility for Compensation under EEOICPA. Report submitted to NIOSH, November 

2004 

Zablotska LB. Comments on the arguments for covering chronic lymphocytic leukemia 

under the Energy Employees Occupational Illness Compensation Program Act of 2000 

(EEOICPA) advanced by its stakeholders in the “Chronic Lymphocytic Leukemia: 

Reconsideration of Exclusion from Eligibility for Compensation under EEOICPA.” 

Report submitted to NIOSH, December 2004