Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation

We examined 277 patients, who have been followed for 1 to 12 years after marrow transplantation, for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, usually cyclophosphamide 50 mg/kg X 4 intravenously, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing 60Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients), usually at increments of 2 to 2.25 Gy/day for 6 to 7 days for cumulative doses of 12 to 15.75 Gy. To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, and 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only (p less than 0.00005), suggesting a significant sparing effect with use of TBI dose fractionation. Addition significant risk factors included the chronic use of steroids posttransplant (highly associated with the presence of chronic graft-versus-host disease), and the diagnoses of acute lymphoblastic or chronic myelogenous leukemia.