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This population-based ecological study analyzes the prevalence of childhood leukemia in Ukraine before and after the Chornobyl nuclear power plant accident, based on the contamination status of the territory, time period, gender, and age. Three regions—Zhytomyr, Kyiv (except Kyiv city), and Chernihiv were included as areas contaminated by radioactive 137Cs from 1 to 15 Ci/km2 with annual effective doses exceeding 1.0 mSv, and Sumy region as the control (non-contaminated) area with 137Cs contamination less than 1 Ci/km2 and effective doses less than 0.5 mSv per year. The integrated database of the National Research Centre for Radiation Medicine used in the present study included 1085 childhood leukemia cases. Two aggregated periods were used for analysis: 1980−1986 (pre-accident) and 1987−2000 (post-accident). ICD-9 codes for leukemia (204−208.9) were used to perform analyses according to the extent of leukemic cells maturity (acute, chronic, and maturity unspecified leukemia), leukemic cell lineage (lymphoid, myeloid and lineage unspecified leukemia) and all leukemia cases in different age subgroups (1−4, 5−9, 10−14, and 15−19 years). Standard methods of descriptive epidemiology were used to calculate the prevalence of disease and frequency ratio in regression models. A statistically significant increase in frequency ratio for acute leukemia (1.44; 95% confidence interval (CI), 1.22−1.71), myeloid leukemia (2.93; 95% CI, 1.71−5.40), cell lineage unspecified leukemia (II) (1.48; 95% CI, 1.18−1.87) and all forms of leukemia (1.59; 95% CI, 1.36−1.86) was found for the post-accident period in highly contaminated areas. The results indicate that the frequency of childhood leukemia (and of some of its types) increased in contaminated areas during the post-accident period, suggesting that radiation exposure after the Chornobyl accident might be the cause of the increase. However, further analytical studies, with individual or at least group dose estimates, are needed to confirm a link between childhood leukemia and the Chornobyl accident.

The recently demonstrated radiation-induction of chronic lymphocytic leukemia (CLL) raises the question as to whether the amount of radiation exposure influences any of the clinical characteristics of the disease. We evaluated the relationship between bone marrow radiation doses and clinical characteristics and survival of 79 CLL cases diagnosed during 1986-2006 in a cohort of 110 645 male workers who participated in the cleanup work of the Chornobyl nuclear accident in Ukraine in 1986. All diagnoses were confirmed by an independent International Hematology Panel. Patients were followed up to the date of death or end of follow-up on 31 October 2010. The median age at diagnosis was 57 years. Median bone marrow dose was 22.6 milligray (mGy) and was not associated with time between exposure and clinical diagnosis of CLL (latent period), age, peripheral blood lymphocyte count or clinical stage of disease in univariate and multivariate analyses. Latent period was significantly shorter among those older at first exposure, smokers and those with higher frequency of visits to the doctor prior to diagnosis. A significant increase in the risk of death with increasing radiation dose was observed (p = 0.03, hazard ratio = 2.38, 95% confidence interval: 1.11,5.08 comparing those with doses ≥22 mGy to doses

Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: < –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

The MDS cases (n=3) among acute radiation syndrome (ARS) survivors after the ChNPP accident were analyzed. MDS diagnoses were based on FAB (1982) and WHO classifications and included the refractory anemia (RA) (patient D. with ARS grade III), refractory anemia with ringed sideroblasts (RARS) (patient B. with ARS grade III), and unclassified MDS (MDS-U) (patient S. with ARS grade I). Clinical management of MDS in ARS patients was analyzed taking into consideration the morphological, immunological, and cytochemical peculiarities of haemopoietic cells. The ARS diagnoses were confirmed in a survey on a regular basis using standard cytogenetic method. Described MDS cases in ARS patients may be the secondary MDS variants taking into consideration possible radiation-induced injuries of hematopoietic cell genome due to the high dose of IR (1.7-5.5 Sv). The possible role of previous irradiation in a range of occupational dose limits before the ChNPP catastrophe for patients D. and B. with ARS grade III, both with possible role of such a confounding factor as petroleum exposure for patient S. (ARS grade I) for the development of MDS cannot be excluded.

Purpose: To present previously unavailable data on the use of stem cell administration to aid recovery of victims of the Chernobyl disaster. On 26 April 1986, an accident at Unit 4 of the Chernobyl Nuclear Power Plant took place during the planned test of one of the safety systems. The diagnosis of acute radiation syndrome (ARS) was confirmed in 134 individuals exposed to high levels of radiation. There were nine patients heretofore unreported in the scientific literature who underwent intraosseous injections of allogeneic bone marrow cells in Kyiv.Conclusions: Transplantation was associated with significantly shortened time to recovery of granulocyte and platelet counts in these patients. While current guidelines would certainly include the use of cytokines, these data provide an indication of the effectiveness of stem cell transplant to treat victims of radiation exposure.

After the Chernobyl accident, the Research Center for Radiation Medicine (RCRM) was established in Kiev (Ukraine). Its main task was to maintain a high level of emergency preparedness and be ready to examine and treat patients who suffer as a result of hypothetical radiation accident. Based on the previous experience, this institution's specialists worked out new diagnostic criteria and drug treatment schemata for acute radiation sickness, created a database on 75 patients with this diagnosis and improved educational programmes for medical students and physicians working in the field of radiation medicine. RCRM collaborates fruitfully with western partners through the joint research projects and connects with the World Health Organization's Radiation Emergency Medical Preparedness and Assistance Network centre. Collaboration with Kiev Center for Bone Marrow Transplantation allows RCRM to use aseptic wards having highly filtered air for the treatment of most severely irradiated patients.

A study of non-cancer effects was based on the data from the State Chernobyl registry of Ukraine. The relative risks of cardiovascular and cerebrovascular diseases are higher in the groups exposed in 250–700 mGy range as compared with the group exposed under 100 mGy. Neurologic and psychological changes rank second and third in structure of morbidity. Relative risks of mortality from circulation diseases were shown to be increased in recovery operation workers of 1986–1987. A case-control study of 14,731 clean-up workers by means non-threshold multi-factor non-linear model has demonstrated a dose-dependent additive-relative risk of radiation cataract being equal to 3.451 (1.347–5.555) per 1 Gy. Changes of proliferative activity of haemopoietic and stromal progenitor cells of exposed in 1986–1987, wavy variations of cellular and humoral immunity parameters were still detected 15–18 years after the exposure.

A 17-year experience of the Research Center for Radiation Medicine (RCRM), Academy of Medical Sciences of Ukraine, on the medical effects of the Chernobyl Nuclear Power Plant accident is reviewed. Results of RCRM in-house studies and international cooperative works are presented. Prospective future directions of international cooperative investigations are considered.

Leukemia is one of the cancers most susceptible to induction by ionizing radiation, but the effects of lower doses delivered over time have not been quantified adequately. After the Chornobyl (Chernobyl) accident in Ukraine in April 1986, several hundred thousand workers who were involved in cleaning up the site and its surroundings received fractionated exposure, primarily from external gamma radiation. To increase our understanding of the role of protracted low-dose radiation exposure in the etiology of leukemia, we conducted a nested case-control study of leukemia in a cohort of cleanup workers identified from the Chornobyl State Registry of Ukraine. The analysis is based on 71 cases of histologically confirmed leukemia diagnosed in 1986-2000 and 501 age- and residence-matched controls selected from the same cohort. Study subjects or their proxies were interviewed about their cleanup activities and other relevant factors. Individual bone marrow radiation doses were estimated by the RADRUE dose reconstruction method (mean dose = 76.4 mGy, SD = 213.4). We used conditional logistic regression to estimate leukemia risks. The excess relative risk (ERR) of total leukemia was 3.44 per Gy [95% confidence interval (CI) 0.47-9.78, P0.01]. The dose response was linear and did not differ significantly by calendar period of first work in the 30-km Chornobyl zone, duration or type of work. We found a similar dose-response relationship for chronic and non-chronic lymphocytic leukemia [ERR = 4.09 per Gy (95% CI0-14.41) and 2.73 per Gy (95% CI0-13.50), respectively]. To further clarify these issues, we are extending the case-control study to ascertain cases for another 6 years (2001-2006).

There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RADRUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of 111 were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects.

Leukemia is one of the early cancers induced by ionizing radiation. Following the Chornobyl accident in Ukraine in April 1986, several hundred thousand workers received fractionated exposure, primarily from external gamma radiation. A nested case-control study of leukemia was performed in a cohort of 110,645 cleanup workers identified from the Chornobyl State Registry of Ukraine during the period 1986 to 2000. A provisional computerized registry of leukemia and 99 related hematological disorders was created through an intensive search of the files of the oncology, hematology and pathology departments within the study area encountering 37,605 possible cases. After linkage and case ascertainment by the international hematology review 111 cases were confirmed as leukemia (87), multiple myeloma (8) and MDS (7). 66.6% of cases and 7.1% of selected controls were deceased. Individual bone marrow doses were estimated using RADRUE method enabling dose reconstruction from the interviews carried out with proxy respondents. Two types of proxies were selected for each deceased subject: a spouse or next-of-kin proxy to provide data on demographic factors and medical history, and to propose co-workers who could serve as proxy respondents regarding the deceased subject’s work history. Detailed interviews were conducted and in 71 case and 501 age- and residence-matched controls selected from the same cohort (mean dose=76.4 (SD=213.4) mGy). In order to reduce uncertainties in the dose estimates, a series of validation studies was undertaken. Conditional logistic regression to estimate leukemia risks. The excess relative risk of total leukemia was 3.44 per Gy (95% confidence interval 0.47– 9.78, p

Objective. From 237 cases of ARS registered after Chornobyl 134 diagnoses were confirmed. The rest of 103 exposed were regarded as non-confirmed ARS (ARS-0) due to the absence of supportive diagnostic materials or other reasons. Long-term follow-up was performed of 192 survivors who are citizens of Ukraine. Methods. Delayed immunologic effects were studied in 57 ARS grade 0-III survivors 20 years after exposure. Cellular immunity was studied by peripheral blood mononuclear cells and early progenitors subset analysis, p53, bcl2, Bax, CD95 expression, spontaneous and verapamil-induced apoptosis, proliferation tests with Con A, microbial and tissue antigens; oxidative status was studied by MDA, catalase, SOD, β-glucosidase, β-galactosidase activity, antioxidant factor, lipid peroxidation, GSH and ceruloplasmin concentration. Results. Combined radiation induced immune deficiency was demonstrated as the early changes with a period of recovery of 7 to 20 years depending of the exposure dose. In ARS-0 and 1 wavy variations of basic immunity parameters were shown with the tendency to normalization. In ARS-1 and 2 (group doses: 1,34; 1,75 Sv) we registered normal mean parameters of T- and B-cell subsets and oxidative status except of ceruloplasmin. Low expression was shown for CD123w antigen. Immune function deviations were demonstrated in activation tests and induced apoptosis. In ARS-3 (mean dose: 5,6 Sv) a marked immune system deficiency was demonstrated at the group levels (low CD4+, NK-cell counts, high CD8+ with significantly smaller cytotoxic T-cell subset) accompanied with low oxidative stress markers and significantly higher MDA and GSH. Analysis of confounding factors such as endocrine and nervous systems influence and blood viral infections carriage showed a prevalent role of the radiation exposurel a marked dose-effect dependency remained at the late period at individual and group levels. Number of TCR-variant cells correlated with the decreased immune function. Radiation-induced depression of immunity was characterized by the non-stability of CD34+ cells with presence of committed primitive early progenitors not capable for terminal differentiation and apoptosis. High proliferative activity and accumulation of CD34+ cells as an adaptive reaction to radiation exposure in combination with the decreased apoptosis, cytotoxic and NK-cell activity could be the basis for radiation-induced oncologic effects.