Chronic myelogenous leukemia and exposure to ionizing radiation — a retrospective study of 443 patients

Abstract

Exposure to ionizing radiations (Rx) has been implicated as a causative factor of chronic myelogenous leukemia (CML). We performed a retrospective study of 443 consecutive CML patients, looking for a history of significant exposure to Rx, and evaluated the clinical and hematological characteristics in order to find any difference between radiation-related CML patients and those with de novo CML. We identified 406 patients without known exposure to mutagens (group I) and 37 patients with prior significant exposure to Rx (group II). In comparison to patients of group I, those of group II showed particular clinical and hematological features: significantly lower incidence of bulky splenomegaly (p < 0.05) and hyperleukocytosis (WBC > 100 x 10(9)/l; p < 0.05); significantly higher incidence of anemia (Hb < 10 g/dl; p < 0.01). Patients with radiation-related CML had a significantly better survival than those with de novo CML (median survival 61 months vs 42 months; p < 0.05). In conclusion, this study of a large cohort of CML patients indicates that the subgroup of patients with a history of significant exposure to ionizing radiation has particular clinical and hematological features at onset (lower tumor burden, higher frequency of anemia) and a better survival.

Natural course and biology of CML

“…Males show an increased incidence of CML at a male/ female ratio of 1.3-1.5:1 [1][2][3]. The only proven risk factor is exposure to high-dose ionising radiation [4]. The average age at presentation is region-dependent.…”

Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib

“…An increased incidence of CML was observed approximately 8 years after the atomic bombings of Hiroshima and Nagasaki (Heyssel et al, 1960). Patients exposed to Thorotrast, an ␣-emitter that was used as a contrast medium in radiology in the 1930s, also have an increased risk of developing CML (Van Kaick et al, 1990), as do patients treated with radiation therapy (Corso et al, 1995). BCR-ABL fusion transcripts can be induced in vitro by high-dose ionizing radiation .…”

Chronic Myelogenous Leukemia

“…Although deletion of a tumor suppressor gene or regulatory region at this site has been postulated, no specific candidate gene has been identified and any potential role of the der(9) deletions in CML pathogenesis remains uncertain. Der (9) deletion is independently associated with adverse outcome in CML-CP patients treated with hydroxyurea and interferon [102,103]. However, it is controversial whether der(9) deletions have prognostic significance in patients treated with imatinib and examination for these deletions is not routine in current diagnostic practice [104][105][106][107].…”

“…There is no known geographic or familial disposition. The only known risk factor associated with the development of CML is ionizing radiation exposure; [8,9] some investigators have also noted a higher incidence in individuals exposed to benzene or alkylating agents [10].…”