Prediction and prevention of transplant-related mortality from pulmonary causes after total body irradiation and allogeneic stem cell transplantation

Between July 1997 and August 2004, 146 consecutive patients with hematologic malignancies received a T cell-depleted peripheral blood stem cell transplant from an HLA-identical sibling by using total body irradiation (TBI) and cyclophosphamide conditioning regimens. Eighty-five patients received 13.6 Gy of TBI with no lung shielding, and 61 received lung shielding (total lung dose, 6-12 Gy). Ninety-four patients (65.5%) had standard-risk disease; the remainder had more advanced disease or unfavorable diagnoses. Of the 21 transplant-related deaths, 14 were from pulmonary causes (10 idiopathic pulmonary syndromes and 4 from infection) that occurred at a median of 90 days (range, 23-238 days) after transplantation. Independent risk factors for pulmonary transplant-related mortality (PTRM) were pretransplantation diffusion capacity for carbon monoxide (relative risk, 5.7 for diffusion capacity for carbon monoxide <85%), smoking (relative risk, 5.0), and CD34 cell dose (relative risk, 9.4 for a CD34 dose of <5 × 106 cells per kilogram). Patients receiving lung shielding had significantly lower PTRM (3.3% versus 14.1%; P = .02) and better overall survival (70% ± 6% versus 52% ± 5%; P = .04), but lung shielding was not a significant independent factor for determining PTRM. These results suggest that pulmonary mortality after TBI-based preparative regimens is predictable and that higher CD34 cell doses can reduce the risk.