Bronchiolitis obliterans after Bone Marrow Transplantation: The Effect of Preconditioning

Abstract

While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-free survival, 2-10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that total body irradiation (TBI) which has been used for pretreatment may influence the subsequent development of BrOb in patients undergoing allogeneic BMT. Since 1976, we have treated 104 patients undergoing allogeneic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 developed chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with BrOb had chronic GVHD. Two of these 4 patients (50%) were alive at the end of 2 years. These data demonstrate that chronic GVHD is a risk factor for BrOb in patients receiving non-TBI preconditioning regimens. The similar incidence of BrOb in this population compared to other studies using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these findings. Allogeneic bone marrow transplantation (BMT) has revolutionized the therapeutic approach toward acute and chronic leukemias, aplastic anemia and rare immunodeficiency disorders. Half of all patients that undergo BMT achieve long-term disease-free survival but a similar number develop significant complications [1]. Prior to the realization of long-term survival in these patients there was an emphasis on the early pulmonary complications of BMT including infectious and noninfectious pneumonitis, acute graft-vs.-host disease (GVHD), chronic aspiration, obstructive airways disease, and pulmonary vascular thrombotic disease [1]. Now with prolonged survival after BMT there is increased attention focused on the relatively late finding of bronchiolitis obliterans (BrOb). BrOb is an obstructive pulmonary disorder affecting the small airways that is associated with connective tissue disease, drug administration, and recently heart-lung transplantation [2,3]. Since 1982, there have been several reports recognizing BrOb to be a late complication of allogeneic BMT [2,4-15]. The etiology of BrOb in these cases is unclear but may in part be due to preconditioning regimens given the results of earlier studies which demonstrated a decline in lung function following TBI [16,17]. We will describe the outcome at our institution of 104 patients that received allogeneic BMTs without TBI preconditioning and compare these results to the experience of other transplant centers where TBI is used in order to determine if preconditioning regimens increase the risk of developing BrOb [2,15].

High-Resolution Computed Tomography of Bronchiolitis Obliterans Syndrome after Bone Marrow Transplantation

“…Several theories have been postulated such as immunologic injury by GVHD [9], viral infections [8,28], decreased IgA levels and chronic aspiration secondary to oesophageal abnormalities [9]. GVHD is most likely to be responsible for the initial mucosal injury, with further damage inflicted from repeated aspiration, opportunistic infections and chemotherapy.…”

Bronchiolitis Obliterans after Allogenic Bone Marrow Transplantation: HRCT Findings

“…Several theories have been postulated, including immunologic injury caused by GVHD (22), viral infection (21, 23), decreased IgA levels, and chronic aspiration secondary to esophageal abnormalities (12). GVHD is most likely to be responsible for the initial mucosal injury, with further damage being inflicted as a result of repeated aspiration, opportunistic infections and chemotherapy (22).…”

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

“…16,22,25,28 The reported case fatality rates vary widely, ranging from 14% to 100% with a mean of 61%. 4,11,[13][14][15]17,19,21,22,27,28,47 In one study of allogeneic HSCT recipients with GVHD, the 3-year mortality rate of those with BO was 65% compared to 44% of those without BO. 14 …”