Late toxicity of total body irradiation with bone marrow transplantation in a rat model

In defined-flora, barrier-maintained rats, radiation nephritis is the principle late toxicity seen after high dose-rate total body irradiation (TBI), when hematologic toxicity is prevented by bone marrow transplantation (BMT). Pneumonitis develops only if rats are placed in a conventional microbiological environment during and after BMT. Low dose-rate TBI gives qualitatively similar late toxicity, but at radiation doses twice as large. Fractionation of the TBI has little effect on the bone marrow ablation doses, but results in increased gastrointestinal and renal tolerance. The addition of immunosuppressive or cytotoxic drugs (cyclosporine-A, methotrexate, cis-platinum) after TBI and BMT greatly decreases the dose of TBI that can be tolerated. The use of a cyclophosphamide plus cytosine arabinoside conditioning regimen prior to TBI and BMT increases the bone marrow ablation dose, but has no effect on acute gastrointestinal toxicity or on renal toxicity. These results indicate that substantial late toxicity may be associated with the TBI conditioning regimens used for BMT even in the absence of cytotoxic and antibiotic drugs, immunosuppressive agents, infection and graft-versus-host disease; and that radiation may be a contributing factor in the nephritis sometimes observed after TBI and BMT.