High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: Treatment technique and related complications

Purpose: Bone marrow transplantation with conditioning regimens that include total-body irradiation (TBI) is widely used in patients with acute lymphoblastic and acute myelocytic leukemias. The major causes of death in this population are relapse of leukemia, infection, and treatment related complications. Our purpose was to achieve a homogenous radiation dose distribution and to minimize the dose to the lungs, liver, and kidneys so that the incidence of organ injury was reduced. Methods and Materials: Dose to the bone marrow, midplane, and periphery was quantified by use of thermoluminescent detectors in a bone-equivalent tissue phantom. In an effort to reduce the risk of complications, we treated relapsed or refractory leukemia patients with TBI administered in fractionated, parallel opposed large fields with 24 MV photons, using tissue compensation and partial- transmission lung shielding. Tissue toxicities were then determined. Results: Dose quantitation in bone-equivalent and tissue-equivalent phantoms demonstrated that backscatter and pair production interactions adjacent to bone increased the bone marrow dose by 6 to 11%. At an SSD of 400 cm and at patient diameters of 20 to 40 cm, the percent inhomogeneity across the phantom with 24 MV photons was 0 to 0.3%, compared to 4 to 6% for 6 MV photons. End-organ toxicities consisted of clinical interstitial pneumonitis in six patients, idiopathic interstitial pneumonitis in three patients, renal toxicity in seven patients, and veno-occlusive disease of the liver in one patient. Toxicities did not correlate with fractionation schedule. Conclusions: Total-body irradiation administered with 24 MV photons increases the dose deposition in bone marrow through pair production and backscatter interactions occurring in bone. Because percent depth dose increases with SSD, the 24 MV beam is more penetrating at a 400 cm distance than at 100 cm and dose homogeneity is improved with higher energies. Thus, the incidence of radiation-mediated injury to lung, liver, and kidney is reduced. This is an effective preparatory regimen for patients with high-risk leukemias requiring bone marrow transplantation.