Risk factors and prognosis of non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation

Non-infectious pulmonary complications (NIPCs) following allogeneic hematopoietic stem cell transplantation (HSCT) are relatively rare, but frequently fatal. This study investigated the pre-transplant risk factors for developing NIPCs using Japanese transplant registry database entries from 2001 to 2009. Among 13,573 eligible patients, 535 experienced NIPCs (3.9%). Multivariate analysis identified high recipient age (60 + years: HR 1.85, P = 0.003), HLA mismatch (HR 1.61, P < 0.001), female to male HSCT (HR 1.54, P < 0.001), and unrelated bone marrow transplantation (UR-BMT) (HR 3.88, P < 0.001) as significantly associated with an increased risk of NIPCs. In contrast, a non-total body irradiation (TBI) regimen with reduced intensity conditioning (RIC) were associated with a decreased risk of NIPCs compared with a cyclophosphamide (CY) + TBI regimen (busulfan + CY: HR 0.67, P = 0.009, other non-TBI: HR 0.46, P < 0.001), fludarabine-based RIC (HR 0.52, P < 0.001), and other RIC (HR 0.42, P = 0.003). The mortality rate was significantly worse for patients with NIPCs than those without (HR 1.54, 71 P < 0.001). This large-scale retrospective study suggests that both allo-reactions to donor cells and conditioning regimen toxicity contributed to NIPCs following HSCT.