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

Abstract

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.

Late effects of blood and marrow transplantation

“…For example, TBI is associated with an increased risk of many late effects such as cardiovascular diseases, COP, hypothyroidism, diabetes, dyslipidemia, infertility, TMA-related kidney injury, bone density loss, avascular necrosis, and secondary solid cancer. 49,54,100,102,114,118,143,159,160 The use of non-TBI conditioning regimens might reduce the burden of these late effects among HCT survivors. Some studies found that cumulative incidences of late effects did not differ much after reduced-intensity regimens compared with myeloablative regimens, 15,161 and reduced-intensity conditioning was associated with a higher risk of recurrent malignancy among patients with myeloid malignancy.…”

Increased non‐relapse mortality due to high‐dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults

“…Among transplant‐related complications that can lead to NRM, IP was significantly increased after HDCA/CY/TBI. A higher incidence of pulmonary complications, such as IP and bronchiolitis obliterans organizing pneumonia, have been reported following myeloablative regimens containing TBI, compared with non‐TBI regimens (Nakasone et al , ). Our study showed that these complications might be more enhanced with the addition of HDCA.…”

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“…Onset time ranges from 5 to 2800 days with a median of 108 days. 6 In a recent review of 9550 allogeneic HSCT recipients, 38 cryptogenic organizing pneumonia was diagnosed in 2% of patients. HLA disparity, femaleto-male HSCT, and peripheral blood stem cell transplant were significantly associated with an increased risk of cryptogenic organizing pneumonia.…”

“…The 3-year nonrelapse mortality rate and overall survival rate in the cryptogenic organizing pneumonia group were 29.0% (95% confidence interval, 20.2%-38.3%) and 60.5% (95% confidence interval, 49.9%-69.5%). 38 The clinical presentation is usually acute or subacute with 2 weeks of fever, nonproductive cough, and dyspnea. Radiologically, findings include patchy (multifocal, diffuse, or focal) consolidations that tend to be peripheral and/or peribronchovascular, ground glass opacities, or nodular lesions.…”