Incidence, outcome, and risk factors of late-onset noninfectious pulmonary complications after unrelated donor stem cell transplantation

Allogeneic hematopoietic cell transplantation (allo-HCT) of older or patients with comorbidities has become possible due to new regimens for reduced-intensity conditioning. The use of fludarabine, carmustine and melphalan as the preparative regimen (FBM) reduces toxicity while providing substantial anti-leukemic activity. Chronic GVHD (cGVHD) of the lung or bronchiolitis obliterans syndrome (BOS) remains a serious non-infectious complication contributing to treatment-related morbidity. We conducted a retrospective analysis of 259 patients (median age: 61.5, range: 24-76 years) transplanted after FBM conditioning to identify and characterize clinical risk factors for developing BOS. The cumulative incidence rate of BOS was 4.2% (95% confidence interval (CI): 2.4-7.6%) at 1 year and 8.5% (95% CI: 5.6-12.9%) at 5 years after allo-HCT with a median follow-up of 36.5 (range: 3-136) months. In multivariate analysis, age o55 years at allo-HCT (who received 25% higher carmustin-dose in preparative regimen), pulmonary complications after allo-HCT and GVHD prophylaxis without in-vivo T-cell depletion (cyclosporine-A/ATG or cyclosporine-A/ alemtuzumab) were associated with BOS. We observed no significant differences in clinical variables such as smoking or lung diseases before allo-HCT. In contrast to cGVHD affecting other organs, BOS showed no impact on overall survival. In conclusion, we identified risk factors associated with developing BOS after conditioning with a reduced toxicity protocol.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation

Duque‐Afonso

Ihorst

Wäsch

et al. 2013

“…Therefore, we cannot evaluate the usefulness of pretransplant PFTs. Although abnormal post-transplant PFTs are also reported to predict LONIPCs, 38 only four patients had abnormal PFTs between allo-HSCT and onset of BO in our cohort. These results indicate that it is difficult to detect airway obstruction before the appearance of respiratory symptoms unless PFTs are more frequent.…”

Section: Discussionmentioning

confidence: 81%

Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic haematopoietic SCT

Ueda

Watadani

Maeda

et al. 2010

Late-onset noninfectious pulmonary complications (LONIPCs) are life threatening for allogeneic hematopoietic SCT (allo-HSCT) recipients. However, the impact of LONIPCs on survival has not been properly evaluated and little is known about treatment efficacy. We retrospectively investigated 290 allo-HSCT recipients in our institute and reviewed the clinical aspects of 44 patients who had been diagnosed with LONIPCs. LONIPCs were significantly associated with higher rates of chronic GVHD (Po0001) and nonrelapse mortality (P ¼ 0.013), and lower rates of relapse (P ¼ 0.009). As a result of these effects, OS was significantly worse in those with LONIPCs (P ¼ 0.003). This result differs from a previous report. We then assessed short-term treatment response and final outcome. These results were defined by radiological findings, subjective symptoms, oxygen requirement and survival. Use of inhaled and systemic steroids did not affect either short-term response or final outcomes. However, administration of systemic corticosteroids earlier than at 21 days (median interval of time from onset of symptoms to systemic corticosteroids administration) was associated with a better outcome (P ¼ 0.054 for short-term response, and 0.016 for final outcome). Our study indicates that LONIPCs reduce OS, and early intervention with systemic corticosteroids may be effective.

“…Almost all of the previous studies were limited to case reports or series that did not include more than 10 cases of COP/BOOP, and/ or did not analyze COP/BOOP independently but rather as a part of late-onset non-infectious pulmonary complications. 6,7,[10][11][12][14][15][16][17] To the best of our knowledge, only one report, from Seattle, has included more than 20 cases (49 cases with COP/BOOP). 8 Thus, we performed a large retrospective study that included about 200 patients with COP/BOOP.…”

Section: Introductionmentioning

confidence: 99%

Pre-transplant risk factors for cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation

Nakasone

Onizuka

Suzuki

et al. 2013

Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P ¼ 0.05), female-to-male HCT (OR 1.53, P ¼ 0.023), and PBSC transplant (OR 1.84, P ¼ 0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P ¼ 0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P ¼ 0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P ¼ 0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n ¼ 19) and 26% (n ¼ 12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.