Scientific Protocol for the Study of Leukemia and Other Hematologic Diseases Among Clean-up Workers in Ukraine Following the Chernobyl Accident
Condition: Leukemia
MeSH terms: Leukemia; Hematologic Diseases
Study type: Observational

Summary: 
      Leukemia holds a special place in the study of radiation-related cancer because bone marrow
      is one of the tissues most sensitive to the carcinogenic effect of ionizing radiation,
      radiogenic leukemia has the shortest latent period among radiation-induced cancers, and its
      appearance suggests that solid tumors may follow. These same characteristics also contribute
      to its considerable significance in radiation protection. There are, nevertheless, important
      gaps in existing knowledge of radiation-induced leukemia, gaps that derive from
      characteristics of the study of the atomic bombing of Hiroshima and Nagasaki, and from
      studies of the effects of medical irradiation and studies of nuclear workers, these being the
      studies that have provided most of the information to date. These gaps include the presumed
      reduction in risk resulting from dose-fractionation and low dose-rate, and the time-response
      function in the first five years after exposure.

      The primary objective of this study is to investigate leukemia risk as a function of such
      radiation; it would constitute the largest epidemiologic study conducted to date among
      working-age males, a group of particular concern in establishing occupational radiation
      safety standards. In addition, data on cases of multiple myeloma and myelodysplasia
      identified in the cohort will be collected to test the hypothesis of a dose related
      association between radiation and increased risk for each of these diseases.

      The primary scientific objectives of the proposed study are to test the following hypotheses:
      (a) that there is a dose-related increase in risk of leukemia among these liquidators; (b)
      that the magnitude of any observed risk per unit dose is less than that seen in the atomic
      bomb survivors, exposed to essentially instantaneous radiation.

      Subsidiary objectives include: (a) to investigate the nature of the dose-response
      relationship among liquidators and to identify modifiers of risk, including time since
      exposure, age at exposure, etc.; (b) to test the hypothesis that there is a dose-related
      increased risk of multiple myeloma; (c) to test the hypothesis that there is a dose-related
      increased risk of myelodysplasial; (d) to collect and store buccal cells from about 2,000
      liquidators with a wide range of dose estimates extending to well over 1 Gy for possible use
      in future molecular studies of their DNA.
    

Detailed description: 
      Leukemia holds a special place in the study of radiation-related cancer because bone marrow
      is one of the tissues most sensitive to the carcinogenic effect of ionizing radiation.
      Radiogenic leukemia has the shortest latent period among radiation-induced cancers, and its
      appearance suggests that solid tumors may follow. These same characteristics also contribute
      to its considerable significance in radiation protection. There are, nevertheless, important
      gaps in existing knowledge of radiation-induced leukemia, gaps that derive from
      characteristics of the study of the atomic bombing of Hiroshima and Nagasaki, and from
      studies of the effects of medical irradiation and studies of nuclear workers; these are the
      studies that have provided most of the information to date. The gaps include the presumed
      reduction in risk resulting from dose-fractionation and low dose-rate, as well as the time-
      response function in the first five years after exposure. The study described herein is
      intended to fill those gaps.

      The Chornobyl accident exposed hundreds of thousands of people to radiation, notably those
      involved in its cleanup operations. The second phase of a case-control study of ionizing
      radiation and leukemia is being conducted in a cohort of approximately 100,000 Ukrainian
      "liquidators" involved in cleanup work following the accident at the Chornobyl Nuclear Power
      Plant in northern Ukraine which occurred on April 26, 1986. The cohort is restricted to
      liquidators who first worked around the power plant between 1986 and 1990 and were residents,
      when first registered in the Chornobyl State Registry, in Kyiv City or in one of five oblasts
      (major civil divisions) that comprise the study area. This cohort, consisting of males of
      working age, received mean bone marrow doses of approximately 80-100 milli-gray (mGy) at low
      to moderate dose rates, with those sent earlier receiving the highest doses. The primary
      objective of this study is to investigate leukemia risk as a function of such radiation; it
      constitutes probably the largest epidemiologic study conducted to date among working-age
      males, a group of particular concern in establishing occupational radiation safety standards.

      The primary scientific objectives of the proposed study are to evaluate whether there is a
      doserelated increase in risk of leukemia among these liquidators, and how it compares with
      the observed risk per unit dose seen in the atomic bomb survivors, exposed to essentially
      instantaneous radiation. A secondary objective is to identify any modifiers of risk,
      including time since exposure, age at exposure, etc.

      The field work for the second phase of the study, with an extended case ascertainment for
      2001 through 2006 has been complated. As a result of the second phase, a total of75 confirmed
      cases of leukemia and 12 cases of multiple myeloma have been ascertained. We are currently in
      the process of database construction, dosimetric calculation for data analyses for leukemia,
      and manuscript preparation.

      The small sub-study on uncertainties associated with human factors is to be started upon
      SSIRB approval.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Ukrainian Chernobyl cleanup workers ("liquidators") approx. 100,000 persons
      
Keywords: Radiation