Technical Report No. 9-91
Differential effects of atomic bomb irradiation in inducing major leukemia types: analyses of open-city cases including the Life Span Study cohort based upon updated diagnostic systems and the Dosimetry System 1986 (DS86)
Tomonaga M, Matsuo T, Carter RL, Bennett JM, Kuriyama K, Imanaka F, Kusumi S, Mabuchi K, Kuramoto A, Kamada N, Ichimaru M, Pisciotta AV, Finch SCSummary
From 1945 through 1980, the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, collected reports of 766 cases of leukemia occurring among the open-city sample of atomic bomb survivors who were within 9 km of the hypocenters at the time of the bombings (ATB). Only 249 of these cases occurred among the Life Span Study (LSS) cohort. In this report we utilize data from the additional 517 cases from the leukemia registry together with the LSS cohort data to study the effects of atomic bomb irradiation on major leukemia types. All available hematological specimens of registered leukemia cases were reviewed. The French-American-British classification and other improved diagnostic methods were used to reclassify cases into 21 categories, including new disease entities such as adult T-cell leukemia (ATL). These categories were then grouped into four major types for analysis: (1) acute lymphocytic leukemia (ALL), (2) acute myeloid leukemia (AML) including myelodysplastic syndromes, (3) chronic myeloid leukemia (CML), and (4) OTHER types including ATL. Analyses of radiation effects were based on the updated Dosimetry System 1986.
Incidence rates of all four leukemia types increased with increasing exposure level. The effects of radiation were significantly greater on the incidence of ALL and CML than on that of AML and OTHER. Exposures <50 mgy=”” apparently=”” produced=”” excess=”” cases=”” of=”” all=”” and=”” cml=”” whereas=”” exposures=””>50 mGy and probably at least 229 mGy were required to produce excesses in AML. This differential effect disappeared in time as incidence rates returned to (or toward) background levels.
In the two lowest dose categories (1-49 and 50-499 mGy), estimated incidence either remained constant or increased slightly as the population of survivors aged. In the two highest dose categories (500-1,499 and greater than or equal to 1,500 mGy), however, estimated incidence rates of all types declined. An excess of AML and ALL, but not of CML and OTHER, remained through the final study period (1976-80) in the greater than or equal to 1,500-mGy dose category.
Among unexposed persons, the estimated risk of CML in Nagasaki relative to Hiroshima was significantly less than that of AML, whereas that of OTHER types was significantly greater, because ATL cases occurred only in Nagasaki. The city effect on background rates appeared to explain the generally higher incidence of leukemia (except for ATL) in Hiroshima.
Also in unexposed persons, incidence in older groups (16-35 years ATB, greater than or equal to 36 years ATB) relative to the youngest group (0-15 years ATB) was less for ALL than AML, but greater for CML and OTHER types than for AML. The risk of ALL remained relatively constant with age ATB, whereas that of AML, and to a greater extent CML and OTHER, increased with age ATB.
The time to onset of ALL, AML, and CML declined with increasing dose. The rate of decline, however, was greater for ALL and CML than for AML. The resulting differences at high doses reflect shorter incubation times for atomic-bomb-induced ALL and CML than for AML.
From 1945 through 1980, the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, collected reports of 766 cases of leukemia occurring among the open-city sample of atomic bomb survivors who were within 9 km of the hypocenters at the time of the bombings (ATB). Only 249 of these cases occurred among the Life Span Study (LSS) cohort. In this report we utilize data from the additional 517 cases from the leukemia registry together with the LSS cohort data to study the effects of atomic bomb irradiation on major leukemia types. All available hematological specimens of registered leukemia cases were reviewed. The French-American-British classification and other improved diagnostic methods were used to reclassify cases into 21 categories, including new disease entities such as adult T-cell leukemia (ATL). These categories were then grouped into four major types for analysis: (1) acute lymphocytic leukemia (ALL), (2) acute myeloid leukemia (AML) including myelodysplastic syndromes, (3) chronic myeloid leukemia (CML), and (4) OTHER types including ATL. Analyses of radiation effects were based on the updated Dosimetry System 1986.
Incidence rates of all four leukemia types increased with increasing exposure level. The effects of radiation were significantly greater on the incidence of ALL and CML than on that of AML and OTHER. Exposures <50 mgy=”” apparently=”” produced=”” excess=”” cases=”” of=”” all=”” and=”” cml=”” whereas=”” exposures=””>50 mGy and probably at least 229 mGy were required to produce excesses in AML. This differential effect disappeared in time as incidence rates returned to (or toward) background levels.
In the two lowest dose categories (1-49 and 50-499 mGy), estimated incidence either remained constant or increased slightly as the population of survivors aged. In the two highest dose categories (500-1,499 and greater than or equal to 1,500 mGy), however, estimated incidence rates of all types declined. An excess of AML and ALL, but not of CML and OTHER, remained through the final study period (1976-80) in the greater than or equal to 1,500-mGy dose category.
Among unexposed persons, the estimated risk of CML in Nagasaki relative to Hiroshima was significantly less than that of AML, whereas that of OTHER types was significantly greater, because ATL cases occurred only in Nagasaki. The city effect on background rates appeared to explain the generally higher incidence of leukemia (except for ATL) in Hiroshima.
Also in unexposed persons, incidence in older groups (16-35 years ATB, greater than or equal to 36 years ATB) relative to the youngest group (0-15 years ATB) was less for ALL than AML, but greater for CML and OTHER types than for AML. The risk of ALL remained relatively constant with age ATB, whereas that of AML, and to a greater extent CML and OTHER, increased with age ATB.
The time to onset of ALL, AML, and CML declined with increasing dose. The rate of decline, however, was greater for ALL and CML than for AML. The resulting differences at high doses reflect shorter incubation times for atomic-bomb-induced ALL and CML than for AML.