Enhanced Renal Toxicity of TotalBody Irradiation Combined with Radioimmunotherapy

Total body irradiation (TBI) with and without additional radioimmunotherapy (RIT) was examined for renal toxicity after stem cell transplantation. Serum creatinine levels of 35 patients (15 female, 20 male, median age 40.5 years, range 17–60 years) after TBI alone and of 23 patients (eight female, 15 male, median age 47, range 16–58 years) after TBI with additional RIT were determined between 10/1997 and 11/1999. TBI was performed by external-beam radiotherapy in six fractions over 3 days with renal doses of 12 Gy in the TBI-alone group and 6 Gy in the group with additional RIT. The mean kidney dose due to the 188Re-radiolabeled antibody was estimated to be 8.3 Gy (2.3–11.6 Gy). Within 12 months after treatment, creatinine levels increased from 77 mmol/l (SD ± 11) to 89 mmol/l (SD ± 20) for TBI alone and from 78 mmol/l (SD ± 13) to 144 mmol/l (SD ± 52) for combined TBI and RIT. Despite a 50% reduction of the external-beam contribution to the kidney dose, the application of approximately 10 GBq 188Re-labeled anti-CD66 monoclonal antibody with a calculated renal dose of 8.3 Gy (range 2.3–11.5 Gy) led to renal toxicity, as reported previously. In the absence of a positive dose-response relationship for the 188Re-labeled antibody, the observation may be explained by an underestimation of the biologically effective dose and the inaccuracy of the dose determination at the glomerular level.