Prognostic Significance of Early Declines in Pulmonary Function After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

BACKGROUND: Pulmonary function test (PFT) impairments are common after allogeneic he-matopoietic stem cell transplantation. The prognostic significance of these declines on outcomes is not well understood. The objectives were to determine the frequency of declines in pulmonary function (FVC, FEV1, and diffusing capacity for carbon monoxide [DLCO ]) in the early post-transplantation period; and to determine the prognostic significance of these declines on mortality or development of bronchiolitis obliterans syndrome. METHODS: This was a retrospective cohort study conducted at Mayo Clinic, Rochester, Minnesota. PFTs were obtained at baseline and at day +100. Competing risk survival models were developed, which accounted for pre-transplantation pulmonary function and relapse status. RESULTS: Between January 1, 2005, and December 31, 2020, 1,145 subjects underwent allogeneic hematopoietic stem cell transplantation and had a pre-transplantation PFT performed. Of these, 900 (78.6%) survived to day 100 and had post-transplantation PFTs performed (median [interquartile range] 97 [94–103] d). A decline of 610% in FEV1, FVC, or DLCO was seen in 401 of 900 subjects (44.5%). Declines of 620% in FEV1 (hazard ratio 1.65, 95% CI 1.07–2.56; P 5 .02), FVC (hazard ratio 1.72, 95% CI [1.11–2.67]; P 5 .02), and DLCO (hazard ratio 1.46, 95% CI 1.04–2.07; P 5 .028) were all associated with reduced survival when compared with those with < 10% decline in PFT meas-ures. These findings were independent of pre-transplantation pulmonary function or relapse sta-tus. Bronchiolitis obliterans syndrome was diagnosed in 118 subjects (10.3%), and there was no relationship between early PFT decline and a subsequent diagnosis of bronchiolitis obliterans syndrome. The subjects who received myeloablative conditioning with cyclophosphamide plus total body irradiation or cyclophosphamide plus fludarabine plus total body irradiation were more likely to have lower spirometry values after hematopoietic stem cell transplantation. The subjects who received reduced intensity conditioning or nonmyeloablative conditioning with flu-darabine plus total body irradiation were more likely to have higher post–hematopoietic stem cell transplantation FEV1, FVC, and DLCO . CONCLUSIONS: An absolute decline of 620% in FEV1, FVC, or DLCO were associated with reduced survival independent of pre-transplantation pulmonary function or relapse status. In contrast to previous work, early declines in PFT measures were not associated with future development of bronchiolitis obliterans syndrome.