Clinical characteristics of chronic lymphocytic leukemia occurring in chornobyl cleanup workers.

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 <22 mGy). After adjustment for radiation dose, survival of CLL cases was significantly shorter among those with younger age at first exposure, higher peripheral blood lymphocyte count, more advanced clinical stage of disease and older age at diagnosis (all p < 0.05). This is the first study to examine association between bone marrow radiation doses from the Chornobyl accident and clinical manifestations of the CLL in Chornobyl cleanup workers. The current study provides new evidence on the association of radiation dose and younger age at first radiation exposure at Chornobyl with shorter survival after diagnosis. Future studies are necessary with more cases in order to improve the statistical power of these analyses and to determine their significance. Copyright © 2016 John Wiley & Sons, Ltd.

Radiation and the risk of chronic lymphocytic and other leukemias among chornobyl cleanup workers.

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.

Hematopoietic cell infusion for the treatment of nuclear disaster victims: new data from the Chernobyl accident.

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.

The Ukrainian-American study of leukemia and related disorders among Chornobyl cleanup workers from Ukraine: III. Radiation risks.

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, P < 0.01]. 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% CI < 0-14.41) and 2.73 per Gy (95% CI < 0-13.50), respectively]. To further clarify these issues, we are extending the case-control study to ascertain cases for another 6 years (2001-2006).