BRONCHIOLITIS OBLITERANS AFTER BONE-MARROW TRANSPLANTATION - THE EFFECT OF PRECONDITIONING

While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-f ree survival, 2-10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that tot al body irradiation (TBI) which has been used for pretreatment may inf luence the subsequent development of BrOb in patients undergoing allog eneic BMT. Since 1976, we have treated 104 patients undergoing allogen eic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 develo ped chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with Br Ob had chronic GVHD. Two of these 4 patients (50%) were alive at the e nd of 2 years. These data demonstrate that chronic GVHD is a risk fact or for BrOb in patients receiving non-TBI preconditioning regimens. Th e similar incidence of BrOb in this population compared to other studi es using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these f indings. Allogeneic bone marrow transplantation (BMT) has revolutioniz ed the therapeutic approach toward acute and chronic leukemias, aplast ic anemia and rare immunodeficiency disorders. Half of all patients th at undergo BMT achieve long-term disease-free survival but a similar n umber develop significant complications [1]. Prior to the realization of long-term survival in these patients there was an emphasis on the e arly pulmonary complications of BMT including infectious and noninfect ious pneumonitis, acute graft-vs.-host disease (GVHD), chronic aspirat ion, obstructive airways disease, and pulmonary vascular thrombotic di sease [1]. Now with prolonged survival after BMT there is increased at tention focused on the relatively late finding of bronchiolitis oblite rans (BrOb). BrOb is an obstructive pulmonary disorder affecting the s mall airways that is associated with connective tissue disease, drug a dministration, and recently heart-lung transplantation [2, 3]. Since 1 982, there have been several reports recognizing BrOb to be a late com plication of allogeneic BMT [2,4-15]. The etiology of BrOb in these ca ses is unclear but may in part be due to preconditioning regimens give n the results of earlier studies which demonstrated a decline in lung function following TBI [16,17]. We will describe the outcome at our in stitution of 104 patients that received allogeneic BMTs without TBI pr econditioning and compare these results to the experience of other tra nsplant centers where TBI is used in order to determine if preconditio ning regimens increase the risk of developing BrOb [2,15].