Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse.

From June 1981 to March 1987, 106 patients--59 with acute myeloid leukemia (AML) and 47 with chronic myelogenous leukemia (CML)--were treated with Cyclophosphamide 60 mg/kg X 2 d and total body irradiation (TBI-990 cGy/3fr/3d described dose) before allogeneic bone marrow transplantation. Seventy-nine patients are evaluable for risk of relapse: 32 with chronic myelogenous leukemia (23 in first chronic phase, 9 in accelerated phase) and 47 with acute myeloid leukemia (38 in first complete remission, 9 in subsequent phases). Actual TBI doses delivered to these patients varied between 839 and 1250 cGy (mean 956 +/- 101)/3 fr/3d, with dose rates between 2.7 and 7.25 cGy/min (mean 4.2 +/- 1.8). Patients receiving high (greater than 990 cGy) and low (less than or equal to 990) dose and/or dose rate (greater than 4 cGy/min and less than or equal to 4, respectively) have been evaluated overall and stratified by type of leukemia and phase of disease. When the patients are considered altogether, high total dose is significantly correlated with decreased risk of relapse (p = 0.0005) as well as high dose rate (p = 0.03). When considering specific subgroups, the influence of total dose on relapse rate is evident both for "early" and "advanced" leukemias, while an impact of dose rate appears only for chronic myelogenous leukemia in 1st chronic phase. Pertinent radiobiological and clinical literature is reviewed, and a possible role of dose fractionation and dose rate in leukemic control rate is evidenced; in this TBI setting, total dose not less than 990 cGy/3fr/3d and dose rate not less than 4 cGy/min have to be guaranteed.