Influence of Pretransplantation Restrictive Lung Disease on Allogeneic Hematopoietic Cell Transplantation Outcomes

Abstract

We conducted a 15-year retrospective cohort study to determine the prevalence of restrictive lung disease prior to allogeneic hematopoietic cell transplant (HCT), and to assess whether this was a risk factor for poor outcomes. 2545 patients were eligible for the analysis. Restrictive lung disease was defined as a total lung capacity (TLC) <80% of predicted normal. Chest x-rays and /or computed tomography scans were reviewed for all restricted patients to determine whether lung parenchymal abnormalities were unlikely or highly likely to cause restriction. Multivariate Cox-proportional hazard and sensitivity analyses were performed to assess the relationship between restriction and early respiratory failure and nonrelapse mortality. Restrictive lung disease was present in 194 subjects (7.6%) prior to transplantation. Among these cases, radiographically apparent abnormalities were unlikely to be the cause of the restriction in 149 (77%) subjects. In unadjusted and adjusted analyses, the presence of pulmonary restriction was significantly associated with a 2-fold increase in risk for early respiratory failure and nonrelapse mortality, suggesting that these outcomes occurring in the absence of radiographically apparent abnormalities may be related to respiratory muscle weakness. These findings suggest that pulmonary restriction should be considered as a risk factor for poor outcomes after transplant.

Evaluating the Impact of Antithymocyte Globulin on Lung Function at 1 Year after Allogeneic Stem Cell Transplantation

“…Restrictive pattern (RP) was defined as a TLC < 80% of the predicted normal and FEV 1 /VC ≥ 0.7 [25]. New airflow obstruction (AFO) was defined according to recently modified NIH guidelines [26, 27]: FEV 1 /VC < 0.7, FEV 1 ≤75% and FEV 1 decrease ≥=10% from the pretransplant level. Patients were defined as having developed early respiratory failure if they required mechanical ventilation for > 24 hours for a non-elective reason.…”

Long-Term Physiological Side Effects After Allogeneic Bone Marrow Transplantation

“…Restrictive lung disease is frequently observed 3 to 6 months after stem cell tranplantation in patients conditioned with TBI, although some patients develop severe late restrictive defects. 34 The most common noninfectious late complications include bronchiolitis obliterans (BO), BO organizing pneumonia, and idiopathic pneumonia syndrome. Chronic obstructive pulmonary disease can be detected in up to 20% of long-term survivors after allo-BMT.…”

Identifying risk factors associated with worse outcomes in adolescents and young adults undergoing hematopoietic stem cell transplantation

“…However, independently, a history of infection was also associated with worse outcomes in our study, and this finding corroborates prior studies . The reason why AYAs undergoing allogeneic HSCT have such a substantial rate of reduced pulmonary function is not clear, but is likely related to adverse effects from previous chemotherapeutic agents, irradiation, or infections during prior therapy . For patients with compromised pulmonary function, therapies with known pulmonary toxicity, such as total body irradiation and busulfan, should likely be dose reduced or avoided as long as alternative strategies can be used to minimize the risk of relapse …”